Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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HRas proto-oncogene, GTPase(HRAS) HRas proto-oncogene, GTPase(HRAS) Related Genes Homo sapiens
CHROMOSOME 11,
CYTOBAND 11p15.5,
ENSEMBL_GENE_ID ENSG00000174775,
GENERIF_SUMMARY The Tg.AC (v-Ha-ras) transgenic mouse model provides a reporter phenotype of skin papillomas in response to either genotoxic or nongenotoxic carcinogens., The Tg.Ac (v-Ha-ras) mouse model was not overly sensitive and possesses utility as an adjunct to the battery of toxicity studies used to establish carcinogenic risk., immunohistochemical analysis reveals a protective effect of H-ras expression mediated via apoptosis in node-negative breast cancer patients, molecular dynamics simulations to show that Ras, a monomeric G protein, can generate mechanical force upon hydrolysis, Point mutations were identified in DNA from two of the 115 normal individuals. Both mutations resulted in an amino acid substitution at position 12 in H RAS., H-Ras/mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblasts, H-Ras mutations at the binding site for the GTP nucleotide ring in a human multiple myeloma line leads to transformation and factor-independent cell growth, HRAS genes are biallelically expressed in multiple fetal and adult tissues both in humans and in mice, overexpression of PPARalpha or the c-Ha-ras transgene is not associated with the liver tumorigenesis induced by DEHP in rasH2 mice, steady-state structure of the switch I region of the protein in both the inactive GDP-bound conformation as in the active GTP-bound conformation., Ha-ras mutations detected in HPV-induced cervical intraepithelial neoplasia grade II and invasive squamous cell carcinoma, Results demonstrate the close relationship between Ha-ras expression level and sensitization of 5-flurouracil (5-FU)-treated cells., using fragments of the human c-Ha-ras gene containing 8-hydroxyguanine (8-OH-G) in codon 12, evidence for the highly complex biochemical events leading to activation of the oncogene, the human c-Ha-ras proto-oncogene product does not influence the androgen-dependence of prostate carcinogenesis due to the probasin-mediated SV40 T antigen., Ras activates the MAP kinase cascade through simultaneous dual effector interactions, When mutated, causes hepatocarcinogenesis in transgenic mice., complete loss of p53 is a prerequisite for collaborating with activated Ha-ras to promote bladder tumorigenesis, H-ras mutations have a role in malignant transformation of aerodigestive spindle cell carcinoma, a domain of Rap1 acts dominantly on COOH-terminal lipid modification of Ha-Ras, which has been considered to be essential and sufficient for the plasma membrane localization, Changes in flexibility upon protein-protein complex formation of H-Ras & the Ras-binding domain of C-Raf1 have been investigated using the molecular framework approach FIRST and molecular dynamics simulations of in total approximately 35 ns length., ras gene alterations have a specific and early role in the development of follicular type of thyroid tumors in Taiwan., Myc rescued cell growth inhibition induced by Ras, RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR., No significant correlations were found between mutations in colorect cancer., H-Ras-specific activation of Rac-MKK3/6-p38 pathway has a role in invasion and migration of breast epithelial cells, the mechanism of O2*-mediated Ras guanine nucleotide dissociation is similar to that of NO/O2-mediated Ras guanine nucleotide dissociation, Ras exists in (at least) two conformational states identifiable by nuclear magnetic resonance spectroscopy, We found mutations in p53, K-ras, and BRAF genes in 35%, 30%, and 4% of tumors, respectively, and observed a minimal or no co-presence of these gene alterations., RAS-MEK-ERK1/2 signaling pathway can sensitize cells to TRAIL-induced apoptosis by up-regulating DR4 and DR5, reduced Ras activation in cells harbouring the Hepatitis C virus subgenomic replicon, K-ras mutations are found in plasma after colorectal tumor resection, the mechanism for Ras-mediated down-regulation of Par-4 is by promoter methylation, Ras isoforms have distinct and separate cellular and subcellular distribution that may persist even in the malignantly transformed state in pancreatic disease, In this study, we probe the cellular and molecular mechanisms of RAS-mediated transformation., HRAS oncogene could play an important role in the development of cervical cancer, in addition to the presence of HPV, by reducing the G1 phase and accelerating the G1/S transition of infected cells, N-Ras(L61) transformed cells lack a G0-G1 arrest upon TGF-beta treatment due to absence of p27., Ras activity regulates Fbw7-mediated cyclin E proteolysis; impaired cyclin E proteolysis is a mechanism through which Ras mutations promote tumorigenesis., RIG1 exerts inhibitory effect at the level of Ras activation, which is independent of Ras subtype but dependent on membrane localization of RIG1. It may be mediated through downregulation of Ras levels and alteration of Ras subcellular distribution., studies provide evidence for the existence of human-specific mechanisms that resist Ras/MEK/ERK-mediated transformation, in primary fibroblasts stabilization of Ras protein by ROS and ERK1/2 amplifies the response of the cells to growth factors and in systemic sclerosis represents a critical factor in the onset and progression of the disease, growth factor-induced, Ras-mediated changes of keratinocyte shape may be an important mechanism that determines the speed of wound epitheli, Germline mutations in HRAS perturb human development and increase susceptibility to tumors., Incidence of K-ras mutation and frequencies of COX-2 and gastrin overexpression are high in laterally spreading granular and protruded type colorectal tumors., We conclude that in wild-type cells, endogenous Ras does not need to be prenylated to be active., IL-24 is a member of IL-10 family of cytokines, and it signals through two hetorodimeric receptors, whose expression is also upregulated by ras oncogenes, K-ras mutation was found in 29% of sporadic adenocarcinomas respectively and in 0% and 22% of the 9 HNPCC cases., Expression of constitutively active Galpha(q)Q209L in cells inhibited Ras activation of the PI3K/Akt pathway but had no effect on Ras/Raf/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] signalling, activation of the PI3K/AKT pathway replaced Ras once tumors formed, although other effectors were still activated independently of Ras, presumably by factors provided upon the establishment of a tumor microenvironment, APC and K-ras, but not CTNNB1 mutations have roles in regulation of expression of hMLH1 in sporadic colorectal carcinomas, Oncogenic RAS activity is directly responsible for OPCML promoter hypermethylation & epigenetic gene silencing. Elevation of the RAS signaling pathway may play an important role in epigenetic inactivation of OPCML in human epithelial ovarian cancer., Analysus if 2502 patients with acute myeloid leukemia at diagnosis for NRAS mutations around hot spots at codons 12, 13, and 61 and correlation of the the results with cytomorphology, cytogenetics, other molecular markers, and prognosis., Ras induces ErbB4 receptor phosphorylation in a non-autocrine manner and this activation depends on multiple Ras effector pathways and on ErbB4 kinase activity., Our data suggest that mutations of PTPN11 as well as RAS play a role in the pathogenesis of not only myeloid hematological malignancies but also a subset of RMS malignancies, Interplay and transmission of structural information between the switch regions are important factors for Ras function. They propose that initiation of GTP hydrolysis sets off the separation of the Ras/effector complex., the H-RAS 81T --> C polymorphism may induce aneuploidy through overexpression of the active p21 isoform of H-RAS, The IGFBP3, hRas, JunB, Egr-1, Id1 and MIDA1 genes were up-regulated in psoriatic involved skin compared with uninvolved skin., intracellular generation of NO* by nNOS leads to S-nitrosylation of H-Ras, which interferes with Raf-1 activation and propagation of signalling through ERK1/2, In 239 Thai adult AML cases, 35 RAS mutations were found in 32 cases (13%) predominantly classified as M1/M2 (53%) followed by M4/M5 (38%). Ten cases were positive for NRAS codon 12, 11 for NRAS codon 61, 13 for NRAS codon 13, and one for KRAS codon 13., Activating RAS mutation is a pivotal molecular lesion that is implicated in the pathogenesis of AML and MDS., Ras mutations were significantly more frequent in inv(16) than in t(8;21) subset (36 versus 8%, P=0.001)., NF1 is a novel regulator of RAS-induced signals in primary vascular smooth muscle cells, There is a signaling loop between Ras-dependent MAPK cascade activation and p73 function., histone deacetylase inhibitor sodium butyrate induces G1/S phase arrest in E1A + Ras-transformed cells through down-regulation of E2F1 activity and stabilization of beta-catenin, Review. An alternative splice form of c-H-ras, called p19ras, is a positive regulator of p73beta via Mdm2. Implications for this previously unidentified means of regulation are discussed in light of tumor suppression and are extended to p53 and p63., K-ras mutations were observed in 68/182 (37.4%) cases of colorectal cancer., ras may be involved in early stages of larynx carcinogenesis and may be activated by other mechanisms different from mutations, such as epigenetic events, Targeted activation of a human oncogenic-ras transgene in rat pancreas can induce carcinomas correspondent to human pancreatic ductal adenocarcinomas., These findings indicate that mechanical strain causes ROS-dependent S-glutathiolation of Ras at Cys118, leading to myocyte hypertrophy via activation of the Raf/Mek/Erk pathway., The entire Ras/Raf/MEK/ERK pathway is activated by intracellular acidosis, indicating that the initiating acid sensor is found at the level of Ras or above., Down-regulation of MIP-1 alpha was not observed following FGFR3 inhibition in MM cells with RAS mutations implicating RAS-MAPK in MIP-1 alpha regulation, Ras and c-Myc play important roles in the up-regulation of nucleophosmin/B23 during proliferation of cells associated with a high degree of malignancy, thus outlining a signaling cascade involving these factors in the cancer cells., Three unrelated Dutch patients with Costello syndrome all have the same mutation, G12S, in HRAS., High prevalence of CIMP-high and K-ras mutations in G-LST, especially in the proximal colon, could strongly suggest that G-LST appearance is associated with a unique carcinogenic pathway., analysis of H-RAS, K-RAS and N-RAS expression in acute myeloid leukemia, Ras expression in cervical keratinocyte cell lines containing stably replicating extrachromosomal HPV-16 consistently diminished anchorage-independent growth (AI), reduced E6 and E7 expression, and caused p53 induction in these cells., Somatic mosaicism for an HRAS mutation causes Costello syndrome., Activation of Ras plays a critical role in modulating the expression of both CXCL10 and CXCR3-B, which may have important consequences in the development of breast tumors through cancer cell proliferation., The hydrolysis of guanosine triphosphate (GTP) by p21(ras) (Ras) has been modeled by using ab initio type quantum mechanical-molecular mechanical simulations. The minimum energy reaction path is consistent with a 2-step mechanism of GTP hydrolysis., Neurofibromin-deficient mouse embryonic fibroblasts (MEFs) and human NF1 tumor cells were more resistant than neurofibromin-expressing cells to apoptosis mediated by two survival pathways, HRAS mutations represent independent but cooperating events to uniparental disomy during embryonic rhabdomyosarcoma development., The activation of HRAS was inhibited by 25.1% or 81.4% in cells cotransfected with wild-type or Golgi-targeted RIG1, respectively., Taken together, the observations indicate that both H-Ras(G12V) and K-Ras4B(G12V) activates non-conventional and perhaps unique effector pathways to induce cytoplasmic vacuolation in glioblastoma cells., Ras and Ral mediate BCR-controlled activation of JUN/ATF2 and NFAT transcription factors, Ras is able to promote monocyte lineage selection via PKC and PDK1., Transfection of U266 cells with constitutively activated H-Ras (Q61L) attenuated ERK1/2 inactivation and dramatically diminished the lethality of statins + UCN-01 regimen., One female patient exhibiting the distal phalangeal creases had a mutation in the HRAS gene., K-ras mutations may play a less important role in the tumorigenesis of ovarian serous tumor of the Chinese patients., The subcellular distribution of K-Ras is driven by electrostatic interaction of the polybasic region of the protein with negatively charged membranes., We identified two known activating and two novel germline HRAS mutations in four patients with an unusual form of congenital myopathy histologically charactered by an excess of muscle spindles., Study identified Crk adapter proteins, Rac1 and H-Ras, but not RhoA or Cdc42 as crucial components of the Helicobacter pylori CagA protein-induced phenotype., The evaluation of a large number of actinic keratoses specimens have found a low gene mutation rate in low-graded AK lesions. p53 mutations rather than p16(INK4a) and/or Ha-ras mutations may be an early event in the development of AK to cutaneous SCC., low rate of RAS-RAF mutations (2/22, 9.1%) observed in Spitz melanocytic nevi suggests that these lesions harbor as yet undetected activating mutations in other components of the RAS-RAF-MEK-ERK-MAPK pathway, De novo germline HRAS (G12A) and KRAS (F156L) mutations in two siblings with short stature and neuro-cardio-facio-cutaneous features., In contrast to C-RAF that requires farnesylated H-Ras, cytosolic B-RAF associates effectively and with significantly higher affinity with both farnesylated and nonfarnesylated H-Ras., BCR/ABL-Y177 plays an essential role in Ras and Akt activation and in human hematopoietic progenitor transformation in chronic myelogenous leukemia, Erf provides a direct link between the RAS/ERK signaling and the transcriptional regulation of c-Myc and suggests that RAS/ERK attenuation actively regulates cell fate, No mutations in HRAS was found in pilocytic astrocytomas., H-Ras mutation defines a molecular subtype of oral carcinoma with favourable outcome and unique biology, a potential key role for activated members of ras family genes in terms of their contribution to the development of nasal polyposis as well as to the hypertrophy of adjacent turbinates., Examination of various growth-regulatory pathways suggested that Bmi-1 overexpression together with H-Ras promotes human mammary epithelial cell transformation and breast oncogenesis by deregulation of multiple growth-regulatory pathways., These data show that a RAS mutation that only perturbs guanine nucleotide binding has similar functional consequences as mutations that impair GTP hydrolysis and causes human disease., These findings suggest that the activation of Ras signaling pathways promotes the generation of brain cancer stem-like cells from p53-deficient mouse astrocytes by changing cell fate and transforming cell properties., Four cases of Costello syndrome had an unusually severe phenotype, associated in three cases with two unusual mutations, c.35G>A, p.G12D in two cases and c.34G>T, p.G12C in the other., the results of HRAS, BRAF and MAP2K1/2 mutation screening in a large cohort of patients with CS and CFC, H-Ras interacts with Spry2-binding partners, c-Cbl and CIN85, in a Spry2-dependent manner., V12 H-Ras oncogenic signaling may contribute to anchorage-independent growth and tumorigenesis by promoting the final cleavage furrow ingression during cytokinesis., Trafficking of H-Ras was examined to determine whether it can enter cells through clathrin-independent endocytosis (CIE)., K-ras mutations were detected in only one of the Hungarian cases; Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047, study reports on two patients with novel HRAS mutations affecting amino acids 58 (T58I) and 146 (A146V), respectively; both patients show many of the physical and developmental problems characteristic for Costello syndrome, Taken together, these results reveal a novel role for fad24 in the repression of NF-kappaB activity and H-ras-mediated transformation., Some smoking characteristics, i.e. being an ex-smoker, frequency and inhalation, may be associated with risk for colorectal cancer characterized by the wild-type KRAS gene, especially in men., Hras mutation is associated with familial non-medullary thyroid carcinoma, The redox sensitive p21Ras-ERK pathway plays a critical role in sensing and delivering the pro-apoptotic signaling mediated by S-nitrosoglutathione., Results correlate P53 status and mutation site/type with nuclear protein accumulation, clinicopathologic variables and data on K-ras mutations and high-level microsatellite instability., high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma., K-RAS and BRAF mutations are a frequent genetic event in our samples of sporadic papillary and medullary thyroid carcinoma., K-ras and p53 genes are altered in Tamoxifen-associated endometrial carcinoma, Study shows that SOS responds to the membrane density of Ras molecules, to their GTP loading and to the concentration of phosphatidylinositol-4,5-bisphosphate, and that the integration of these signals potentiates the release of autoinhibition., Report extremely weak tumor-promoting effect of troglitazone on splenic hemangiosarcomas in rasH2 mice induced by urethane., RAS signalling may play an important role in neuronal susceptibility to Sindbis virus infection, p19(ras) interaction with p73beta amplifies p73beta-induced apoptotic signaling responses including Bax mitochondrial translocation, cytochrome c release, increased production of reactive oxygen species and loss of mitochondrial transmembrane potential., p21 Ras/Imp regulate cytokine production and migration in CD4 T cells, Presence of K-ras mutations might be associated with lack of response to panitumumab alone and inferior survival in patients with metastatic colorectal cancer., Scribble is an important mediator of MAPK signalling and cooperates with H-ras to promote cell invasion., k-ras may have a role in progression of rectal cancer after resection, K-Ras mutations have a role in treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy, Low-penetrant RB allele in small-cell cancer shows geldanamycin instability and discordant expression with mutant ras., HRAS-shRNA could efficiently down-regulate the expression of H-ras, induce apoptosis of SACC-M cells and simultaneously inhibit cell proliferation., Occupational exposure to coking oven emissions increases expression levels of P21 and P53 proteins in peripheral white blood cells., LDLs stimulate p38 MAPKs and wound healing through SR-BI independently of Ras and PI3 kinase, transfection of a promoterless K-ras cDNA resulted in a significant decrease in endogenous K-ras in a dose- and time-dependent manner and induces pancreatic cell apoptosis, This review will summarize the chemical biology of Ras and discuss in more detail the biophysical and structural features of the membrane bound C-terminus of the protein., the H-RAS T81C polymorphism might be a low penetrance gene predisposition factor for gastric cancer in the Chinese population, Ca(2+) may activate Ras signaling pathway by interaction with Ras, providing clues to understand the role of calcium in regulating Ras function in physiological environments., This study revealed S100A8/A9 genes as candidate markers for metastatic potential of breast epithelial cells., The secondary structure of membrane-bound, lipidated Ras is similar to that determined for the nonlipidated truncated Ras protein for the highly conserved G-domain., Hdm2 is expressed in pancreatic cancer cells as a result of activated Ras signaling, and regulates cellular proliferation and the expression of target genes by p53-independent mechanisms., Costello syndrome-associated HRAS mutations result in prolonged signal flux in a ligand-dependent manner, Ras transformation has at least two independent actions to disrupt E-cadherin junctions, with effects to cause both mislocalization of E-cadherin away from the cell surface and profound decrease in the expression of E-cadherin, The increased accumulation of miR-143 inhibits the proliferation of transfected cells, and results in down-regulation of K-ras protein in colorectal carcinoma., RAS mutations may play a greater role in leukemogenesis than currently believed, The oncoprotein Ras is a possible mediator of Tax-induced apoptosis protection and suggest a possible role of Tax in Ras activation., failed to find hRAS mutations in bladder tumor samples, The Snail-p53 binding as the new therapeutic target for K-Ras-mutated cancers including pancreatic, lung, and colon cancers., Women with the NAT2 fast acetylator genotype may exhibit a higher risk of CRC with increased occurrence of K-RAS mutation., Subtle deficits in inhibition and enhanced excitation evoke the interneuronal changes in the synRas transgenic mouse cortex., K-RAS point mutations, and anomalies of p16-RB1-cyclin D pathway could occur before LOH on 10q23 (PTEN) and microsatellite instability during tumor progression., p21(Ras)-mediated survival signaling is regulated by via a PI(3)K-AKT pathway, which is dependent upon both PDK1 and PKCdelta, and PDK1 activates and regulates PKCdelta to determine the fate of cells containing a mutated, activated p21(Ras)., Rho mediates various phenotypes of malignant transformation by Ras and Src through its effectors, ROCK and mDia [review], A single patient with somatic mosaicism for a Costello syndrome causing HRAS mutation is reported. The male-to-male transmission was from father to son., BLNK recruits active H-Ras to the BCR complex, which is essential for sustained surface expression of BCR in the form of the cap and for the signal leading to functional ERK activation, A novel regulatory mechanism whereby turnover of both endogenous and overexpressed H-Ras protein is controlled by beta-TrCP-mediated ubiquitylation, proteasomal degradation and the Wnt/beta-catenin signaling pathway, is reported., These findings support the hypothesis that the Ras/Raf/Mek/Erk pathway may be constitutively active even in pancreatic tumor cells that express wild-type K-ras., EGFR expression and KRAS mutation status is predictive for clinical response to matuzumab +/- paclitaxel in patients with advanced NSCLC., K-ras mutations, significantly associated with the mucin-secreting type of adenocarcinoma, consistently predict lack of response in white patients, Data show that the combination with CA 19-9 assay is useful for detection and prognostic evaluation of pancreatic carcinoma., Alcohol consumption is weakly associated with an increased risk of having a K-ras mutated pancreatic ductal adenocarcinoma, Study provides evidence that p53, binding with Snail, is exported from a K-Ras-mutated cell through a vesicle transport-like mechanism, independently using a p53-nuclear-exporting mechanism., K-ras, EGFR, and BRAF mutations are disproportionately seen in adenocarcinomas of lung with a dominant micropapillary growth pattern compared with conventional adenocarcinoma in our institutional experience., Chronic NF-kappaB activation delays RasV12-induced premature senescence of human fibroblasts by suppressing the DNA damage checkpoint response., Mutation E17K/AKT1 was not detected in the 24 samples of retinoblastoma analyzed. K-RAS mutations were identified in two samples. There were no mutations in any of the other genes analyzed., HRAS mutation may be a marker of Spitz naevus, The median pancreatic cancer survival in K-ras positive group was 7.0+/-2.4 months and in K-ras negative group was 10.0+/-0.6 months, DEP-1 inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases, BMI1 collaborates with H-RAS to induce an aggressive and metastatic phenotype with the unusual occurrence of brain metastasis., KRAS does not seem an "a priori" negative factor for TKI-based treatment of NSCLC, results suggest that RAS is an important member in the PI3K-AKT signaling and could play an important role in the tumorigenesis of oral carcinoma., Sorafenib inhibits NSCLC cell growth by targeting B-RAF in cells with wild-type KRAS and C-RAF in those with mutant KRAS., Data show that in the presence of negative feedback, changes in the rate of Ras-c-Raf binding have little effect on ERK activation., Investigated the prevalence of PTPN11, HRAS, KRAS, NRAS, BRAF, MEK1, and MEK2 mutations in a relatively large cohort of primary embryonal Rhabdomyosarcoma (RMS) tumors. HRAS and KRAS were found to be rarely mutated., Findings show that JNK is necessary for oncogenic H-ras-induced, caspase-independent cell death, and that both PI3K and Rac1 activities are required for JNK activation and cell death., Data show that significant K-ras mutation occurs most frequently in the pancreatobiliary regions of patients with AIP., the organophosphorous pesticides parathion and malathion induced malignant transformation of breast cells through genomic instability altering p53 and c-Ha-ras, We noted statistically significant difference in genotype distribution at hexanucleotide locus and at SNP 81 T>C between healthy population and colon cancer patients, Data show that conversion of Ras-expressing keratinocytes from a premalignant to malignant state induced by decreasing E-cadherin function was associated with and required an approximately two to threefold decrease in RalA expression., Results show a cooperative relationship between the expression of Ras and loss of RB in providing a discrete proliferative advantage under physiologically relevant conditions., Data suggest that investigation of the mechanisms of abnormal RAS and phosphoinositide-3 kinase pathway activation in erythroblasts may contribute to the understanding of the molecular pathogenesis of PV., HRAS codon 12 mutation is not a very common event in actinic keratosis or nonmelanoma skin cancers, A single cellular event for mutations arising in male germ cells that show a paternal age effect; screening of 30 spermatocytic seminomas for oncogenic mutations in 17 genes identified 2 mutations in FGFR3 and 5 mutations in HRAS., Silencing of the Lats2 tumor suppressor overrides a p53-dependent oncogenic stress checkpoint and enables mutant H-Ras-driven cell transformation., RAS enables DNA damage- and p53-dependent differentiation of acute myeloid leukemia cells in response to chemotherapy, H-ras expression in immortalized keratinocytes produces an invasive epithelium in cultured skin equivalents, Data show that Myc repressed Ras-induced senescence, and that Cdk2 interacted with Myc at promoters, where it affected Myc-dependent regulation of genes, including those of proteins known to control senescence., Screening for BRAF, RET, KRAS, NRAS, and HRAS mutations, as well as RET-PTC1 and RET-PTC3 rearrangements, was performed on cases of Hashimoto thyroiditis with a dominant nodule, loss of BRCA1 function may contribute to the aggressiveness of Ras-MAPK driven breast cancer with associated increase in levels of cyclin D1 and c-myc, enhanced MAPK activity, angiogenic potential & invasiveness, Exogenous expression of RASSF1A is able to induce growth inhibition effect and apoptosis in nasopharyngeal carcinoma cell lines, and this effect could be enhanced by activated K-Ras., p19 induces FOXO1 that in combination with the G1/S phase delay and hypophosphorylation of both Akt and p70SK6 leads to maintenance of a reversible cellular quiescence state, thereby preventing entry into apoptosis., Features of KRAS mutations in lung cancer and contrast these with the features of EGFR mutations., The identification of mutations outwith previously described hotspot codons increases the K-Ras mutation burden in colorectal tumours by one-third., The present study suggests that the single-clonal convergence of K-ras mutation is associated with the malignant progression of intraductal papillary mucinous neoplasms., In Chinese patients with CRC, EGFR mutations were rare, and K-ras mutations were similar to those of Europeans., Oncogenic K-Ras and its effector Raf1 convert death receptors into invasion-inducing receptors by suppressing the ROCK/LIM kinase pathway, and this is essential for K-Ras/Raf1-driven metastasis formation., JNK2 collaborates with other oncogenes, such as Ras, at multiple molecular levels to promote tumorigenesis, increased binding of DNMT3b to E-cadherin promoter region by K-Ras cause promoter hypermethylation for reduced expression of E-cadherin, leading to the decreased cell aggregation and increased metastasis of human prostate cancer cells., Ras induces ARC in epithelial cancers, and ARC plays a role in the oncogenic actions of Ras, Using lung cell lines expressing oncogenic K-Ras, authors show that NF-kappaB is activated in these cells in a K-Ras-dependent manner and that NF-kappaB activation by K-Ras., maintain colorectal cancer cell proliferation during ERK MAP kinases inhibition, Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS., X-ray crystal structure analyses of a series of mutant H-Ras and M-Ras in complex with guanosine 5'-(beta,gamma-imido)triphosphate (GppNHp), representing various intermediate states of the transition, were determined., Leukotriene B(4) BLT receptor signaling regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of Ras/Raf/ERK/p42 AUF1 pathway, Mutations may predict the biological nature of pulmonary adenocarcinomas and facilitate new therapies., investigation of whether HRAS is involved in development of vestibular schwannomas not associated with an underlying NF2 mutation; no potentially pathogenic HRAS mutations found; conclude that HRAS is not a common cause of vestibular schwannomas, Recent studies on the cooperative molecular mechanisms by which p53 inactivation and oncogenic Ras converge to enhance tumorigenesis., The HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude., H-ras was altered in 22% of the oral squamous cell carcinoma samples from a Serbian population. Statistical association with tumour natural history was poor, indicating high clonal heterogeneity and multiple pathways of carcinogenesis., Abolishing the expression of cyclin D1, Cdk4 or Nek2 in MCF10A human mammary epithelial cells expressing H-Ras(G12V) abrogated Ras-induced centrosome amplification., HBP1 targets P16(INK4A), upregulating its expression and consequently is involved in Ras-induced premature senescence., Mutation analysis of K-ras protooncogene in colorectal adenocarcinomas and polyps in Russian patients, Gene amplification and overexpression of H-ras is the major mechanism that causes drug resistance of 5-8F/Erbitux cells to cetuximab., Data show that p66(Shc) coordinates Ras-dependent control of proliferation and anchorage sensation., The presence of a K-ras mutation in cytology specimens distinguishes pancreatic cancer frm cholangiocarcinomain this study., The homozygous type of major allele TT was more frequent in GC group than ChG group, while the frequencies of heterozygous type TC and homozygous type of minor allele CC were higher in ChG group than GC group., We show the shift of Ras into its "off" conformation, which inhibits the Ras pathway; down-regulation of Ras signaling by changes in the Ras-Raf effector interaction;& down-regulation of Ras signaling pathway by catalyzing GTP hydrolysis., An association exists between TRAIL resistance to apoptosis in human pancreatic and lung cancer cell lines and G12D K-ras(12) mutation., Ras is a key mediator of IL-1beta-induced NF-kappaB and HIF-1alpha activation, under normoxia., We therefore conclude that HRAS mutation analysis may be a useful diagnostic tool to help differentiate between Spitz nevus and Spitzoid melanoma., Conformational states of human rat sarcoma (Ras) protein complexed with its natural ligand GTP and their role for effector interaction and GTP hydrolysis., There are novel p53 mutations in gastric cancer and mutation patterns of p53 and k-ras in the population of the central southern region of China., Ras mutational status is associated with resistance to EGFR inhibitors in colorectal carcinoma., gene expressions were significantly higher in the cancer group and may serve as reliable biomarkers to monitor tumour development and the efficiency of therapy, The frequency of EGFR mutation in Chinese non-small cell lung cancer patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite., miR-181a may function as an oral squamous cell carcinoma suppressor by targeting on K-ras oncogene., the implication of H-Ras and NADPH oxidase-generated superoxide production in MMP-13 gene regulation by IL-1beta and TNF-alpha, HRAS1 polymorphism is associated with breast cancer., Cyst fluid K-ras mutation correlates with other markers of aggressive cyst behavior., these data demonstrate that the activation of H-Ras and the downstream molecule Rac1 correlates with EGF-induced breast cancer cell invasion., Ras/Raf/MAPK and RhoA/ROCKII signalling pathways are abnormally activated in eutopic endometrial stromal cells of patients with endometriosis, Taken together, our data indicate that K-Ras mutations are relatively uncommon in cervical cancer but seem to be associated with more advanced tumor stage, increased risk of distant metastases, and poor probability of long-term survival., HRAS1 polymorphism is not associated with breast cancer., findings show activation of H-ras by mutation plays a less frequent role than other genetic events in the development of most transitional cell tumors of the bladder in Kashmiri population, this work identifies the C-terminal HVR, two consecutive proline residues Pro173 and Pro174, as a critical domain that contributes to activation of H-Ras and its invasive potential in human breast epithelial cells., constitutively active H-Ras can confer resistance to anti-EGFR therapy in cancer cells, Novel ectodermal findings were noted in individuals with p.G13C, including loose anagen hair, easily pluckable with a matted appearance, different from the tight curls typical for most Costello syndrome individuals and long eye lashes requiring trimming, RASSF1A has a tumor suppressive effect as a modulator for ROS production induced by oncogenic K-Ras., Data show that the Ras/PI3K/Akt pathway can account for Fyn over-expression in cancers., CDKN2A/ARF, RAS and TP53, but not BRAF, PTEN, MAPK2 or EGFR may have roles in rare salivary gland tumours, HRAS T81C polymorphism is associated with urinary bladder cancer., G-CSF-induced MMP-2 upregulation and invasive phenotype is mediated by Rac1., data demonstrate that SNPs and point mutations observed in HRAS do not change the amino acid sequence, and suggest that the mutations affecting the amino acid sequence may be a rare event in oral carcinomas of the Japanese population., Regulation of Double Strand Break repair by EGFR involves both the NHEJ and HR pathway, and appears to occur in most tumor cell lines regardless of p53 and K-Ras mutation status., A rare case of pancreatic carcinosarcoma in a 48-year-old man in which the sarcomatous component had an identical mutation (G to A transition) at codon 12 of K-ras gene., Genetic K-ras alterations were rather low in the Tunisian population, but further study is necessary to unravel the molecular background of CRC., both EGFR and HRAS mutations are rare events in the carcinogenesis of cutaneous squamous cell carcinoma, and therefore, only a small subgroup of patients will benefit from the screening for mutations, Transformed cells with an activated Ras signaling pathway are therefore particularly susceptible to human cytomegalovirus infection., The H-Ras-ERK-induced and HO-1-mediated pathway could protect renal cancer cells from apoptosis., These results suggest that mutant K-Ras acts in concert with CDK5 and its activators to increase malignant progression, migration, and invasion of pancreatic cancer cells., HRAS mutations and llelic loss of susceptibility loci are associated with familial non-medullary thyroid cancer., identification of an HRAS mutation c.34G>A, predicting a p.G12S amino acid substitution, in the surviving brother of a previously reported sibling pair with Costello syndrome and documentation of same change in autopsy material from his deceased sister, NADPH oxidase NOX4 is a critical mediator in oncogenic H-RasV12-induced DNA-damage response and subsequent senescence., Our findings suggest that the HRAS mutations identified in Costello syndrome (CS) are sufficient to cause oncogene-induced senescence and that cellular senescence might therefore contribute to the pathogenesis of CS., Solution structure of the state 1 conformer of GTP-bound H-Ras protein and distinct dynamic properties between the state 1 and state 2 conformers., The HRAS G-quadruplexes behave as transcription repressors., the HRAS G12V mutation increased cell migration and invasion, mediated by Rac1, along with the mesenchymal morphology obtained through the epithelial-mesenchymal transition, At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well., Helicobacter pylori infection may increase the expression of c-H-ras p21 early in the process of gastric carcinogenesis, triple-negative cases had a worse prognosis for relapse and death, compared with cases with EGFR, KRAS, or ALK mutations or group B triple-negative cases, Mutations of HRAS are associated with Skin tumors induced by sorafenib., The dermatological features of Costello syndrome, a Ras dysregulation syndrome, share many features with cutaneous paraneoplastic syndromes. This may provide further insight into the role of Ras signalling in cutaneous paraneoplastic syndromes., hRas mutations did not appear to be associated with urothelial carcinoma development after kidney transplantation., Data show that PDEdelta activity augments K/Hras signalling by enriching Ras at the plasma membrane., Mutations in hras proteins are present in benign lichenoid keratosis., RET mutations may have a role in medullary thyroid carcinoma, while BRAF, AKT1, and CTNNB1 do not; the role of HRAS, KRAS, and NRAS mutations are not determined, Data show that MiR-181d may act as a glioma suppressor by targeting K-ras and Bcl-2., EGFR and K-ras mutations frequently occur randomly in multifocal lung adenocarcinomas, The data amassed in last several years indicate that the anti-EGFR antibody is ineffective when KRAS has mutated.[review], No significant influence of age was found on the prevalence of K-ras mutation. Males with pathological changes and females with poorly differentiated tumors displayed GAT as a less common genotype compared with most other prevalence studies., The activating point mutations of HRAS in Costello syndrome shift the balance toward the active, signal transmitting state, resulting in dysregulation of the signaling pathway., Genetic alterations in SMAD4 and K-ras in Serbian patients with endometrial carcinoma., In HRAS, two hotspot mutations in codon 12 and eight new genetic alterations were detected in oral squamous cell carcinoma., Findings indicate that Ras-induced nuclear accumulation of activated MEK1/2 was reliant on downregulation of the spatial regulator Sef., reduced C4ST-1 expression and chondroitin sulfation imbalance mediating the effects of oncogenic HRAS signaling in the pathogenesis of Costello syndrome., A total of 80.8% of Chinese patients with colorectal cancer show variations in microsatellite DNA, p53, APC or K-ras., Generation of cetuximab-resistance in 5-8F/Erbitux cells is associated with amplification and overexpression of the H-ras gene., Activating K-ras mutation is one of the frequently encountered molecular alterations that occur in the pathogenesis of pancreaticobiliary malignancy., we have analyzed the prevalence of somatic mutations in the FGFR3, PIK3CA, AKT1, KRAS, HRAS, and BRAF genes in bladder cancers, H-Ras activity is differently regulated by the various mutant p53 categories in tumor cell lines., EFVPTC 2 patients had RAS mutations., COLD-PCR is a highly sensitive, reliable, and convenient clinical assay for H-ras mutation detection in bladder cancer., Transmission of the mutation underscores its attenuated phenotype compatible with reproduction, The polymorphism of H-ras and L-myc genes is not related to colorectal cancer risk, but there is a synergy between H-ras and L-myc polymorphisms in the development of rectal cancer., GSK3beta plays an essential role in Ras degradation and inhibition of this degradation pathway by aberrant Wnt/beta-catenin signaling may contribute to Ras-induced transformation in colorectal tumorigenesis, molecular, clinical, and pathological findings in patients with mutations predicting HRAS p.Gly12Val, activating RAS somatic mutations leading to mosaicism result in benign Keratinocytic epidermal nevi (KEN) of the skin., H-Ras transformation promotes tumor progression by enhancing growth factor receptor signaling as a result of increased receptor macropinocytosis., Studies indicate that mutations of TP53 and Ras proteins were found in cutaneous squamous cell carcinomas (SCCs) cells., The GTP bound state 1 crystal structures of wild-type H-Ras together with the oncogenic G12V and Q61L mutants., study examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases, The consequence of complex formation is a DiRas3-mediated recruitment and anchorage of C-RAF to components of the membrane skeleton, suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase activity., These results suggest that rs12628 C homozygosis of the HRAS gene may be considered a potential risk factor for melanoma development in the North American population, Mosaicism for HRAS c.37G>C and KRAS c.35G>A mutations was found in two individuals with Schimmelpenning syndrome., ). Abnormal methylation of the HRAS gene may be an early event during urocystic tumorigenesis and may be further used as a cancer biomarker in bladder tissue for early diagnosis and a potential therapeutic target., In advanced NSCLC, the presence of K-RAS mutations identifies a subgroup of patients who do not respond to EGFR-TKI therapy., endogenous IL-1beta play a role in elastin gene upregulation and this upregulation is mediated by the Ras-ERK1/2 pathway in 3D cultures, Upregulation of NKG2D ligands by H-RasV12 increased sensitivity of cells to NK cell-mediated cytotoxicity, A novel interplay between K-ras and H-ras, with possible implications for colorectal carcinogenesis., It was concluded that extracellular kinase-mediated up-regulation of c-myc by K-Ras or B-Raf oncogenes disrupts the establishment of apical/basolateral polarity in colon epithelial cells independently of its effect on proliferation., RAS mutations are frequent events in sporadic medullary thyroid cancer., S-nitrosylation of H-Ras at Cys(118) and the activation of Src kinase are spatiotemporally linked events of the S-nitrosothiol-mediated signaling pathway that occurs at the plasma membrane and at the Golgi., K-Ras mutations were present in 89 patients (32.6%)., possible role of K- ras mutation as an early event in the process of endometrial carcinogenesis in type 1 tumors, HRAS p.G12C and p.G12D mutations found in 2 patients with severe neonatal Costello syndrome., the Ras-PI3K signaling pathway targets specific epigenetic modifications in tumor cells, The mutation frequencies of K-ras genes in Taiwanese CRC patients are very low, which may suggest that they are not the dominant factors for CRC occurrence and prognosis in Taiwanese CRC patients., Ras oncoproteins transfer from melanoma to T cells, including tumor-infiltrating lymphocytes (TILs), and subsequently induce functional effects in the adopting T cells., Results show that postzygotic HRAS mosaicism affects epithelial progenitor cells resulting in mutated cells with variable developmental potential. Nevus marginalis appears to be a manifestation of this., The Ras/MEK/ERK pathway might be activated by VEGF and play a critical role in the angiogenesis of chronic subdural hematoma., The results confirm a strong correlation between activating RAS mutations and nevus sebaceus., The findings confirm the predominance of HRAS mutations in nevus sebaceus (NS) and provide evidence that HRAS and KRAS mutations are sufficient to cause NS without genome instability, LOH, or secondary mutation., Fendiline significantly mislocalizes K-Ras and inhibits K-Ras signaling., HRAS T81C SNP has been found to moderately increase thyroid cancer risk with variant alleles implicated more in follicular thyroid tumors, The absence of K-ras gene mutations questions its role in the pathogenesis of gastric cancer and peptic ulcer disease in Indian patients., The prevalence of RAS mutations in the present series of medullary thyroid cancer (MTC) was 10.1%, and 17.6% when considering only RET-negative cases. RAS mutations were found in MTC tumor tissue but not in peripheral blood indicating their somatic origin, Data suggest that EPI64A and B, which are ubiquitously expressed members of the EPI64 subfamily, inactivate Ras and certain Rabs at the periphery of cells., Approximately 90% of medullary thyroid cancers had mutually exclusive mutations in RET, HRAS, and KRAS, suggesting that RET and RAS are the predominant driver pathways in medullary thyroid cancer., Mutation in HRAS gene is not associated with phenytoin induced gingival overgrowth., mutant K-Ras contributes to the maintenance of the aberrantly high levels of survivin in tumors by regulating its stability, and the ability of mutant K-Ras to induce malignant transformation is, in part, dependent on these high levels of survivin., We suggest that disrupted HRAS reagibility, as we demonstrate for the p.E63_D69dup mutation, is a previously unappreciated molecular pathomechanism underlying Costello syndrome., Phacomatosis pigmentokeratotica is best explained by a postzygotic-activating HRAS mutation in a multipotent progenitor cell that gives rise to both a sebaceous and a melanocytic nevus., Dynamic palmitoylation links cytosol-membrane shuttling of acyl-protein thioesterase-1 and acyl-protein thioesterase-2 with that of proto-oncogene H-ras product and growth-associated protein-43, A correlation between the specific Costello syndrome-causing HRAS mutation and severity of medical problems in the affected individual., The ability of K-Ras to activate MST2 and MST2-dependent apoptosis is determined by the differential activation kinetics of mutant K-Ras and wild type K-Ras., Data suggest that mutations in HRAS are relatively common (6/28 patients, 21%, p.Gln61Arg or p.Gln61Lys substitution) in subjects with partially-encapsulated or well-circumscribed follicular variant of papillary thyroid carcinoma in Boston area., study used NMR to obtain detailed mechanistic data on RAS cycling defects conferred by oncogenic mutations, or full-length RASopathy-derived regulatory proteins, Wild-type copies of HRas, NRas and KRas play unique roles in the context of mutant KRas-driven tumors., HRas signal transduction promotes hepatitis C virus cell entry by triggering the host CD81-CLDN1 complex formation., Data suggest that RAS mutations are infrequent in patients with myelodysplastic syndrome that identify subset of patients with higher WBC count and higher bone marrow blast burden., Endomembrane H-Ras controls vascular endothelial growth factor-induced nitric-oxide synthase-mediated endothelial cell migration., These results implied that nicotinamide might be a potential therapeutic agent for human pancreatic cancer treatment through downregulating SIRT1, K-Ras and P-Akt expression., study elucidates a novel correlation between the tumor suppressor gene p53 and the oncogene Ras in regulating EMT program, and expands the knowledge about the function of p53 in EMT process, This study identifies HRAS mutations in deep penetrating nevi. The presence of HRAS mutations and absence of GNAQ or GNA11 mutations in deep penetrating nevi suggests classification of these nevi within the Spitz rather than the blue nevus category., beta4 integrin rs8669 genotyping may help to identify a subgroup of HER-3-negative, K-RAS wild-type colorectal cancer patients who are more likely to benefit from anti-EGFR treatment., Data suggest that HRAS mutations are associated with sporadic pheochromocytoma and paraganglioma; this study in Sweden identified three new somatic mutations in HRAS exomes (G13R, Q61K, Q61R) exclusively in males with pheochromocytoma/paraganglioma., Data indicate that numerous proteins that are up-regulated in H-ras(G12V) transgenic rat pancreatic ductal adenocarcinoma (PDAC) are also up-regulated in human PDAC; therefore, this rat model can be used for diagnostic biomarkers for this disease., OHT induced K-Ras degradation in breast, colon, glioma, and pancreatic cancer cells., Data suggest a treatment rationale for Src- or Ras-activated cancer., Suggest that activating mutations of EGFR, HRAS, and KRAS contribute to the pathogenesis of human seborrheic keratosis., Tunneling nanotubes connecting B and T cells provide a hitherto undescribed route for the transfer of plasma membrane patches containing, for example, H-Ras from B to T cells., Among 30 breast tumors, 10(33%) had BCSCs with AKT1, HRAS, or PIK3CA mutations. A single mutation was detected in HRAS.Tumors in which BCSCs have defects in PI3K/Akt signaling are significantly more likely to manifest nodal metastases., Data indicate oncogenic HRAS (HRAS(G12V)) as a potent mediator of SLC5A8 silencing in human nontransformed normal mammary epithelial cell lines and in mouse mammary tumors through DNMT1., In silico results showed conformational changes in H-RAS that could influence its activation by Sos and phosphate binding, H-ras is one of the genes targeted by miR-663, These results provide evidence for a role of H-ras oncogene in the metabolic reprogramming of MCF10A cells during early mammary carcinogenesis., Finding of somatic activating HRAS and NRAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation., the central role of Ras signaling in enamel formation in Costello syndrome patients, 293 cells transformed with H-Ras enhanced Enteric human adenoviruses replication by more than threefold., HRAS mutations confer erlotinib resistance in head and neck squamous cell culture., HRAS p.G12S mutation has a role in causing woolly hair and epidermal nevi, Results suggest that mosaicism for oncogenic HRAS mutations may increase the risk for developing bladder cancer at a young age., HRAS mutations are associated with proliferative thyroid lesions., Data suggest that mutations in HRAS (as seen in Costello syndrome) affect intrinsic kinetic mechanisms of HRAS and alter HRAS-binding characteristics of GTP/GDP, p120GAP (RAS p21 protein activator), and Cdc25 (guanine nucleotide-releasing factor)., Differences in the regulation of K-Ras and H-Ras isoforms by monoubiquitination., Levels of de novo HRAS mutations in the paternal germline affected by intrinsic mutation rate and selfish selection., there were no significant differences between HRAS mutation positive and mutation negative cases of epithelial-myoepithelial carcinomas in terms of age, gender and outcome., PIK3CA mutations/amplification, HRAS mutation, or PTEN loss that likely lead to PI3K pathway activation were identified in 34 of 75 cases (45%) and did not correlate with disease specific survival., Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5).extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1., activating mutations in HRAS are involved in sporadic nevus spilus that may progress to melanocytic neoplasms, H-Ras gene analysis identified an hypermethylated CpG island in intron 1 that can affect the DNA-protein interaction modifying RNA polymerase II (RNAPII) activity., H-Ras forms dimers on membrane surfaces via a protein-protein interface., Mutations in Ha-ras gene is associated with liver tumors., Case Report, HRAS mutations play a critical role in the genesis of rhabdomyosarcoma, Ras(V12)-mediated oncogenic transformation induces RRAD epigenetic inactivation, which in turn promotes glucose uptake and may contribute to ovarian cancer, Somatic H-RAS mutations are restricted to a relevant proportion of sporadic pheochromocytoma., Oncogenic HRAS in head and neck squamous cell cancer promotes activation of ERK signaling, which in turn mediates cetuximab resistance, Ras expression negatively regulated the TSH-stimulated CREB phosphorylation but was ineffective on forskolin-stimulated CREB phosphorylation, Our study further suggests that the PLA/AT activity of H-rev107 may play an important role in H-rev107-mediated RAS suppression, Trichilemmomas commonly harboured activating HRAS mutations., In OCCS, missense mutations in HRAS were found in 10 of 79 cases (12.66%), and were significantly associated with tumor grade., BLT2 is markedly up-regulated by oncogenic Ras and promotes epithelial-mesenchymal transition in response to TGF-beta in mammary epithelial cells., Data suggest that H-Ras inhibits TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through downregulation of surface death receptors DR4/DR5., We present the case of a patient, in whom fetal tachycardia, polyhdramnios and physical characteristics led to an early diagnosis of Costello syndrome., Patients with somatic mutations, especially HRAS-mutations, have a significantly worse prognosis than patients lacking these changes, H-ras-mediated transformation stimulates vesicular emission of this histone-bound oncogene, which may interact with non-transformed cells., Next-generation sequencing identified recurrent mutations in HRAS (Q61R) in 3 of 5 Inverted urothelial papilloma (IUP), described for the first time in this neoplasm., RAS mutations in indeterminate thyroid nodules have a role in follicular variant of papillary thyroid carcinoma, Case Report, acylation state of Ras proteins (H-Ras and N-Ras) controls not only their distribution between the Golgi apparatus and the plasma membrane, but also their distribution within the Golgi stacks., CARD9 regulates H-Ras activation by linking Ras-GRF1 to H-Ras, which mediates Dectin-1-induced extracellular signal-regulated protein kinase (ERK) activation and proinflammatory responses when stimulated by their ligands., human cellular models with inducible expression of c-Myc and H-RasV12 (Ras), two commonly deregulated oncoproteins operating in a functionally connected signaling network, is reported., Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP activity toward Ras and Rap GTPases., Ecdysoneless and H-Ras expressing human mammary epithelial cells form tumors in NOD/SCID mice., We have demonstrated that clinically achievable concentrations of zoledronic acid and docetaxel cause a reduction in the prenylation of both H-Ras and Rho A and a reduction of protein movement into the membrane., In the presence of Raf1, the RasQ61L mutant has a rigid switch II relative to the wild-type and increased flexibility at the interface with switch I, which propagates across Raf-Ras binding domain., Data indicate that the farnesyl may determine small GTPase K-Ras4B function in different membrane microdomain environments., H-Ras mediates the inhibitory effect of epidermal growth factor on the epithelial Na+ channel, NORE1A allows Ras to qualitatively modify p53 function to promote senescence., MTH1 expression is required for effective transformation of epithelial cells by oncogenic HRAS., The data suggest a role for redox-dependent activation of wild-type KRAS through cysteine 118 in oncogenic HRAS-driven tumorigenesis., Strongly increased HRAS(Gly60Asp) binding to RAF1., ABL phosphorylates tyrosine 137 of H-, K-, and NRAS., The RAS-binding domain of human BRAF protein exhibits allosteric conformational changes upon binding HRAS., RAS-positive thyroid nodules, especially in older individuals, frequently demonstrate a benign phenotype.Cytologically benign nodules, even if RAS-positive, may be candidates for a non-operative observational strategy, Nanoclustering of mutant proteins in plasma membrane dictates downstream effector recruitment, MAPK-activity, and tumorigenic cell proliferation., Expression of flotillin-1 was associated with H-Ras in breast cancer, especially in TNBC (p < 0.001)., HRAS differentially influences iTBS- and PAS-induced LTP., Data show that Ba/F3 cells transformed with mutant HRAS protien indicated equal sensitivity towards Map kinase kinase (MEK) and mTOR serine-threonine kinase (mTOR) inhibition., analysis of HRAS, KRAS and NRAS expression in colorectal tumor cells, Ras.GDP weakly binds to the catalytic but not to the allosteric site of Sos., Phenotypic Screening Identifies Protein Synthesis Inhibitors as H-Ras-Nanocluster-Increasing Tumor Growth Inducers., SHP2 activity is elevated in astrocytes isolated from glioblastoma multiforme-prone H-Ras(12V) knock-in mice., We describe extensively the tumor suppressive and oncogenic roles of miRNAs in regulation of ras oncogenes in Oral squamous cell carcinoma, Endocytosis separates EGF receptors from endogenous fluorescently labeled HRas and diminishes receptor signaling to MAP kinases in endosomes., our data suggest roles for HRAS and EGFR as drivers in a subset of poroma and porocarcinoma.,
OFFICIAL_GENE_SYMBOL HRAS,
OMIM_DISEASE Bladder cancer, somatic, Spitz nevus or nevus spilus, somatic, Nevus sebaceous or woolly hair nevus, somatic, Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic, Thyroid carcinoma, follicular, somatic, Congenital myopathy with excess of muscle spindles, Costello syndrome,
SP_COMMENT disease:Defects in HRAS are a cause of bladder cancer [MIM:109800]., disease:Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]. CMEMS is a variant of Costello syndrome., disease:Defects in HRAS are the cause of Costello syndrome [MIM:218040]; also known as faciocutaneoskeletal syndrome. Costello syndrome is a rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities., disease:Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC)., disease:Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma [MIM:607464]; also known as Hurthle cell thyroid neoplasia. Hurthle cell thyroid carcinoma accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms., disease:Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors., enzyme regulation:Alternate between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP)., function:Ras proteins bind GDP/GTP and possess intrinsic GTPase activity., mass spectrometry: PubMed:9020151, mass spectrometry:Includes one nitric oxide molecule PubMed:9020151, PTM:Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi., PTM:S-nitrosylated; critical for redox regulation. Important for stimulating guanine nucleotide exchange. No structural perturbation on nitrosylation., similarity:Belongs to the small GTPase superfamily. Ras family., subcellular location:Shuttles between the plasma membrane and the Golgi apparatus., subunit:In its GTP-bound form interacts with PLCE1. Interacts with TBC1D10C. Interacts with RGL3 (By similarity). Forms a signaling complex with RASGRP1 and DGKZ. Interacts with RASSF5.,