Genomes and Genes
Gene Symbol: H-Ras
Description: HRas proto-oncogene, GTPase
Alias: C-BAS/HAS, C-H-RAS, C-HA-RAS1, CTLO, H-RASIDX, HAMSV, HRAS1, RASH1, p21ras, GTPase HRas, GTP- and GDP-binding peptide B, Ha-Ras1 proto-oncoprotein, Harvey rat sarcoma viral oncogene homolog, Harvey rat sarcoma viral oncoprotein, Ras family small GTP binding protein H-Ras, c-has/bas p21 protein, c-ras-Ki-2 activated oncogene, p19 H-RasIDX protein, transformation gene: oncogene HAMSV, transforming protein p21, v-Ha-ras Harvey rat sarcoma viral oncogene homolog
- Swarthout J, Lobo S, Farh L, Croke M, Greentree W, Deschenes R, et al. DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras. J Biol Chem. 2005;280:31141-8 pubmed..Hence, DHHC9.GCP16 displays the properties of a functional human ortholog of the yeast Ras palmitoyltransferase. ..
- Li Q, Mattingly R. Restoration of E-cadherin cell-cell junctions requires both expression of E-cadherin and suppression of ERK MAP kinase activation in Ras-transformed breast epithelial cells. Neoplasia. 2008;10:1444-58 pubmed
- Denayer E, Parret A, Chmara M, Schubbert S, Vogels A, Devriendt K, et al. Mutation analysis in Costello syndrome: functional and structural characterization of the HRAS p.Lys117Arg mutation. Hum Mutat. 2008;29:232-9 pubmed..Together, 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. ..
- Gupta S, Ramjaun A, Haiko P, Wang Y, Warne P, Nicke B, et al. Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Cell. 2007;129:957-68 pubmed..Most importantly, they are highly resistant to endogenous Ras oncogene-induced tumorigenesis. The interaction of Ras with p110alpha is thus required in vivo for certain normal growth factor signaling and for Ras-driven tumor formation. ..
- Porat Shliom N, Kloog Y, Donaldson J. A unique platform for H-Ras signaling involving clathrin-independent endocytosis. Mol Biol Cell. 2008;19:765-75 pubmed..Arf6 stimulation of macropinocytosis also involves passage through the distinct lipid phases, but recruitment of Akt is not observed. ..
- Tsai F, Shyu R, Jiang S. RIG1 inhibits the Ras/mitogen-activated protein kinase pathway by suppressing the activation of Ras. Cell Signal. 2006;18:349-58 pubmed..This inhibition of Ras activation may be mediated through downregulation of Ras levels and alteration of Ras subcellular distribution. ..
- Castro P, Soares P, Gusmao L, Seruca R, Sobrinho Simoes M. H-RAS 81 polymorphism is significantly associated with aneuploidy in follicular tumors of the thyroid. Oncogene. 2006;25:4620-7 pubmed..Our results suggest that the H-RAS 81T --> C polymorphism may induce aneuploidy through overexpression of the active p21 isoform of H-RAS. ..
- Bacher U, Haferlach T, Schoch C, Kern W, Schnittger S. Implications of NRAS mutations in AML: a study of 2502 patients. Blood. 2006;107:3847-53 pubmed..However, there was a trend to better survival in most subgroups, especially when other molecular markers (FLT3-LM, MLL-PTD, and NPM) were taken into account. ..
- Zhang Y, Jin M, Liu B, Ma X, Yao K, Li Q, et al. Association between H-RAS T81C genetic polymorphism and gastrointestinal cancer risk: a population based case-control study in China. BMC Cancer. 2008;8:256 pubmed publisher..These findings indicate, for the first time, that there is an H-RAS T81C polymorphism existing in Chinese population, and this SNP might be a low penetrance gene predisposition factor for gastric cancer. ..
- Catela Ivkovic T, Loncar B, Spaventi R, Kapitanovic S. Association of H-ras polymorphisms and susceptibility to sporadic colon cancer. Int J Oncol. 2009;35:1169-73 pubmed..013) but not in allelic distribution. At SNP 81 T>C statistically significant difference in distribution of both genotypes (p=9.15x10(-6)) and alleles (p=2.77x10(-6)) was found. No differences were found between genders. ..
- Sahu R, Batra S, Kandala P, Brown T, Srivastava S. The role of K-ras gene mutation in TRAIL-induced apoptosis in pancreatic and lung cancer cell lines. Cancer Chemother Pharmacol. 2011;67:481-7 pubmed publisher..This study demonstrates an association between TRAIL resistance to apoptosis in human pancreatic and lung cancer cell lines and G12D K-ras(12) mutation. ..
- Membrino A, Cogoi S, Pedersen E, Xodo L. G4-DNA formation in the HRAS promoter and rational design of decoy oligonucleotides for cancer therapy. PLoS ONE. 2011;6:e24421 pubmed publisher..The G4-decoys repressed HRAS transcription and caused a strong antiproliferative effect, mediated by apoptosis, in T24 bladder cancer cells where HRAS is mutated. ..
- Rocks O, Peyker A, Kahms M, Verveer P, Koerner C, Lumbierres M, et al. An acylation cycle regulates localization and activity of palmitoylated Ras isoforms. Science. 2005;307:1746-52 pubmed..The de/reacylation cycle also initiates Ras activation at the Golgi by transport of PM-localized Ras guanosine triphosphate. Different de/repalmitoylation kinetics account for isoform-specific activation responses to growth factors. ..
- Shin I, Kim S, Song H, Kim H, Moon A. H-Ras-specific activation of Rac-MKK3/6-p38 pathway: its critical role in invasion and migration of breast epithelial cells. J Biol Chem. 2005;280:14675-83 pubmed
- Lim K, Counter C. Reduction in the requirement of oncogenic Ras signaling to activation of PI3K/AKT pathway during tumor maintenance. Cancer Cell. 2005;8:381-92 pubmed..Thus, as tumorigenesis progresses the addiction of cancers to their initiating oncogene is reduced to, at least in the case of Ras, the PI3K/AKT pathway. ..
- Makrodouli E, Oikonomou E, Koc M, Andera L, Sasazuki T, Shirasawa S, et al. BRAF and RAS oncogenes regulate Rho GTPase pathways to mediate migration and invasion properties in human colon cancer cells: a comparative study. Mol Cancer. 2011;10:118 pubmed publisher..This study discriminates oncogene-specific cell migration and invasion pathways mediated by Rho GTPases in colon cancer cells and reveals potential new oncogene-specific characteristics for targeted therapeutics. ..
- Jeong M, Bae J, Kim W, Yoo S, Kim J, Song P, et al. p19ras interacts with and activates p73 by involving the MDM2 protein. J Biol Chem. 2006;281:8707-15 pubmed..Alternative splicing of the proto-oncogene H-ras pre-mRNA has led to two distinct transcripts, p19ras and p21ras. In both endogenous and overexpressed systems, we confirmed that p19ras binds to full-length p73beta in vivo and ..
- Jin T, Ding Q, Huang H, Xu D, Jiang Y, Zhou B, et al. PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus. Cell Res. 2012;22:661-76 pubmed publisher..Collectively, this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQR11. ..
- Min J, Zaslavsky A, Fedele G, McLaughlin S, Reczek E, De Raedt T, et al. An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB. Nat Med. 2010;16:286-94 pubmed publisher..These studies define the mechanism by which two major pathways can be simultaneously activated in metastatic prostate cancer and establish EZH2 as a driver of metastasis. ..
- Gripp K, Stabley D, Nicholson L, Hoffman J, Sol Church K. Somatic mosaicism for an HRAS mutation causes Costello syndrome. Am J Med Genet A. 2006;140:2163-9 pubmed..This is the first reported CS patient mosaic for the common HRAS mutation, likely due to a somatic mutation occurring very early in fetal development. ..
- Tsai F, Shyu R, Jiang S. RIG1 suppresses Ras activation and induces cellular apoptosis at the Golgi apparatus. Cell Signal. 2007;19:989-99 pubmed..The proapoptotic activities of RIG1 are mediated through the activation of caspase-2 and -3 and are independent of its effect on RAS. ..
- Vernitsky H, Rechavi O, Rainy N, Besser M, Nagar M, Schachter J, et al. Ras oncoproteins transfer from melanoma cells to T cells and modulate their effector functions. J Immunol. 2012;189:4361-70 pubmed publisher..In conclusion, our findings demonstrate a hitherto unknown phenomenon of intercellular transfer of Ras oncoproteins from melanoma to TILs that consequently augments their effector functions. ..
- Kim J, Kim W, Jeong M, Jang S, Song K, Park S, et al. p19(ras) amplifies p73beta-induced apoptosis through mitochondrial pathway. Biochem Biophys Res Commun. 2008;373:146-50 pubmed publisher..These results have important implications for understanding the molecular events of p19(ras) to p73 functions in cancer cells. ..
- Fischer A, Hekman M, Kuhlmann J, Rubio I, Wiese S, Rapp U. B- and C-RAF display essential differences in their binding to Ras: the isotype-specific N terminus of B-RAF facilitates Ras binding. J Biol Chem. 2007;282:26503-16 pubmed..Taken together, these data suggest that the activation of B-RAF, in contrast to C-RAF, may take place both at the plasma membrane and in the cytosolic environment. ..
- Spaargaren M, Bischoff J. Identification of the guanine nucleotide dissociation stimulator for Ral as a putative effector molecule of R-ras, H-ras, K-ras, and Rap. Proc Natl Acad Sci U S A. 1994;91:12609-13 pubmed..Furthermore, we show that RalGDS-RBD and the Ras-binding domain of Raf-1 compete for binding to the Ras-like GTPases. These data indicate that RalGDS is a putative effector molecule for R-ras, H-ras, K-ras, and Rap. ..
- Serrano M, Lin A, McCurrach M, Beach D, Lowe S. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997;88:593-602 pubmed..Negation of ras-induced senescence may be relevant during multistep tumorigenesis. ..
- Morrison D, Cutler R. The complexity of Raf-1 regulation. Curr Opin Cell Biol. 1997;9:174-9 pubmed..The picture clearly emerging is that Raf-1 activity can be regulated by multiple mechanisms. ..
- Ebinu J, Bottorff D, Chan E, Stang S, Dunn R, Stone J. RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs. Science. 1998;280:1082-6 pubmed..RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calcium concentrations to Ras activation. ..
- Vos M, Ellis C, Elam C, Ulku A, Taylor B, Clark G. RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor. J Biol Chem. 2003;278:28045-51 pubmed..Thus, we identify RASSF2 as a new member of the RASSF1 family of Ras effectors/tumor suppressors that exhibits a specificity for interacting with K-Ras. ..
- Guil S, de la Iglesia N, Fernandez Larrea J, Cifuentes D, Ferrer J, Guinovart J, et al. Alternative splicing of the human proto-oncogene c-H-ras renders a new Ras family protein that trafficks to cytoplasm and nucleus. Cancer Res. 2003;63:5178-87 pubmed..This observation suggests that p19 and p21 play differential and complementary roles in the cell. ..
- Pacold M, Suire S, Perisic O, Lara Gonzalez S, Davis C, Walker E, et al. Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma. Cell. 2000;103:931-43 pubmed..These unique Ras/PI3Kgamma interactions are likely to be shared by PI3Kalpha. The complex with Ras shows a change in the PI3K conformation that may represent an allosteric component of Ras activation. ..
- Vos M, Ellis C, Bell A, Birrer M, Clark G. Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis. J Biol Chem. 2000;275:35669-72 pubmed..Thus, the RASSF1 tumor suppressor may serve as a novel Ras effector that mediates the apoptotic effects of oncogenic Ras. ..
- Jones C, Kipling D, Morris M, Hepburn P, Skinner J, Bounacer A, et al. Evidence for a telomere-independent "clock" limiting RAS oncogene-driven proliferation of human thyroid epithelial cells. Mol Cell Biol. 2000;20:5690-9 pubmed
- Li W, Han M, Guan K. The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf. Genes Dev. 2000;14:895-900 pubmed..Sur-8 interacts with Ras and Raf and is able to form a ternary complex with the two proteins. Thus, Sur-8 may function as a scaffold that enhances Ras-MAP kinase signal transduction by facilitating the interaction between Ras and Raf. ..
- Houlston R, Tomlinson I. Polymorphisms and colorectal tumor risk. Gastroenterology. 2001;121:282-301 pubmed..58, 95% confidence interval [CI]: 1.21-2.07); Harvey ras-1 variable number tandem repeat polymorphism (HRAS1-VNTR; OR = 2.50, 95% CI: 1.54-4.05); and methylenetetrahydrofolate reductase (MTHFR)(Val/Val) (OR = 0...
- Reuther G, Der C. The Ras branch of small GTPases: Ras family members don't fall far from the tree. Curr Opin Cell Biol. 2000;12:157-65 pubmed..First, the three Ras proteins may not be functionally identical. Second, Ras function involves functional cross-talk with their close relatives. ..
- Lin A, Barradas M, Stone J, Van Aelst L, Serrano M, Lowe S. Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling. Genes Dev. 1998;12:3008-19 pubmed..Consequently, constitutive MAPK signaling activates p53 and p16 as tumor suppressors. ..
- Ortiz Vega S, Khokhlatchev A, Nedwidek M, Zhang X, Dammann R, Pfeifer G, et al. The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1. Oncogene. 2002;21:1381-90 pubmed..The preferential ability of RASSF1A to heterodimerize with Nore and thereby associate with Ras-like GTPases may be relevant to its putative tumor suppressor function. ..
- Vanhaesebroeck B, Welham M, Kotani K, Stein R, Warne P, Zvelebil M, et al. P110delta, a novel phosphoinositide 3-kinase in leukocytes. Proc Natl Acad Sci U S A. 1997;94:4330-5 pubmed..Possible selective functions of p110delta in white blood cells are discussed. ..
- Johne A, Roots I, Brockmoller J. A single nucleotide polymorphism in the human H-ras proto-oncogene determines the risk of urinary bladder cancer. Cancer Epidemiol Biomarkers Prev. 2003;12:68-70 pubmed..51; P = 0.002). In general, 81CC occurred more frequently in advanced types of bladder cancer. We conclude that individuals harboring the homozygous 81C-genotype of the H-ras proto-oncogene are at an increased risk of bladder cancer. ..
- Rodriguez Viciana P, Warne P, Vanhaesebroeck B, Waterfield M, Downward J. Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation. EMBO J. 1996;15:2442-51 pubmed..These data show that PI 3-kinase is regulated by a number of mechanisms, and that Ras contributes to the activation of this lipid kinase synergistically with tyrosine kinases. ..
- Taparowsky E, Suard Y, Fasano O, Shimizu K, Goldfarb M, Wigler M. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature. 1982;300:762-5 pubmed..The functionally significant difference between the transforming and normal genes appears to be a single base mutation, which produces an amino acid change in the sequence of the proteins that the genes encode. ..
- Joneja U, Vranic S, Swensen J, Feldman R, Chen W, Kimbrough J, et al. Comprehensive profiling of metaplastic breast carcinomas reveals frequent overexpression of programmed death-ligand 1. J Clin Pathol. 2017;70:255-259 pubmed publisher..These results can be exploited in clinical trials using immune checkpoint inhibitors. ..
- Kim M, Jeon M, Oh H, Park S, Kim T, Shong Y, et al. <i>BRAF</i> and <i>RAS</i> mutational status in non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive subtype of encapsulated follicular variant of papillary thyroid carcinoma in Korea. Thyroid. 2018;: pubmed publisher..The presence of a <i>RAS</i> mutation is not helpful for preoperative differentiation between NIFTPs and invasive EFVPTCs. ..
- Cappuzzo F, Toschi L, Finocchiaro G, Ligorio C, Santoro A. Surrogate predictive biomarkers for response to anti-EGFR agents: state of the art and challenges. Int J Biol Markers. 2007;22:S10-23 pubmed
- Kreeger P, Wang Y, Haigis K, Lauffenburger D. Integration of multiple signaling pathway activities resolves K-RAS/N-RAS mutation paradox in colon epithelial cell response to inflammatory cytokine stimulation. Integr Biol (Camb). 2010;2:202-8 pubmed publisher..This success arises from a quantitative integration of multiple pro-apoptotic (pIkappaBalpha, pERK2) and pro-survival (pJNK, pHSP27) signals in manner not easily discerned from intuitive inspection. ..
- Kolokoltsova O, Domina A, Kolokoltsov A, Davey R, Weaver S, Watowich S. Alphavirus production is inhibited in neurofibromin 1-deficient cells through activated RAS signalling. Virology. 2008;377:133-42 pubmed publisher..This work highlights novel host cell determinants required for alphavirus pathogenesis and suggests that RAS signalling may play an important role in neuronal susceptibility to SINV infection. ..
- Koh M, Yong H, Kim E, Son H, Jeon Y, Hwang J, et al. A novel role for flotillin-1 in H-Ras-regulated breast cancer aggressiveness. Int J Cancer. 2016;138:1232-45 pubmed publisher..001). Our findings provide insight into the molecular basis of Ras isoform-specific interplay with flotillin-1, leading to tumorigenicity and aggressiveness of breast cancer. ..
- Li Y, Peng Y, Jiang X, Cheng Y, Zhou W, Su T, et al. Whole exome sequencing of thymic neuroendocrine tumor with ectopic ACTH syndrome. Eur J Endocrinol. 2017;176:187-194 pubmed..Somatic mutations of three potential tumor-related genes (HRAS, PAK1 and MEN1) might contribute to the tumorigenesis of thymic neuroendocrine tumors with EAS. ..
- Zhang H, Liu J, Fu X, Yang A. Identi?cation of Key Genes and Pathways in Tongue Squamous Cell Carcinoma Using Bioinformatics Analysis. Med Sci Monit. 2017;23:5924-5932 pubmed
- Wang L, Zhao Y, Xiong Y, Wang W, Fei Y, Tan C, et al. K-ras mutation promotes ionizing radiation-induced invasion and migration of lung cancer in part via the Cathepsin L/CUX1 pathway. Exp Cell Res. 2018;362:424-435 pubmed publisher..This study will provide cathepsin L as a potential target for tumor therapy. ..
- Zhai B, Yang H, Mancini A, He Q, Antoniou J, Di Battista J. 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. J Biol Chem. 2010;285:23568-80 pubmed publisher..We conclude that LTB(4) may support the resolution phase of the inflammatory response by stabilizing COX-2, ensuring a reservoir of ambient pro-resolution lipid mediators. ..
- Batista W, Ogata F, Curcio M, Miguel R, Arai R, Matsuo A, et al. S-nitrosoglutathione and endothelial nitric oxide synthase-derived nitric oxide regulate compartmentalized ras S-nitrosylation and stimulate cell proliferation. Antioxid Redox Signal. 2013;18:221-38 pubmed publisher..The nonparticipation of Src kinase and the localized production of NO by endothelial NO synthase at the plasma membrane limited NO-mediated Ras activation to the plasma membrane. ..
- Willard M, Willard F, Li X, Cappell S, Snider W, Siderovski D. Selective role for RGS12 as a Ras/Raf/MEK scaffold in nerve growth factor-mediated differentiation. EMBO J. 2007;26:2029-40 pubmed..These data suggest that RGS12 may play a critical, and receptor-selective, role in coordinating Ras-dependent signals that are required for promoting and/or maintaining neuronal differentiation. ..
- Fritsch R, de Krijger I, Fritsch K, George R, Reason B, Kumar M, et al. RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms. Cell. 2013;153:1050-63 pubmed publisher..These findings revise our understanding of the regulation of type I PI3K by showing that both RAS and RHO family GTPases directly regulate distinct ubiquitous PI3K isoforms and that RAC activates p110? downstream of GPCRs. ..
- Li F, Munchhof A, White H, Mead L, Krier T, Fenoglio A, et al. Neurofibromin is a novel regulator of RAS-induced signals in primary vascular smooth muscle cells. Hum Mol Genet. 2006;15:1921-30 pubmed
- Aylon Y, Ofir Rosenfeld Y, Yabuta N, Lapi E, Nojima H, Lu X, et al. The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1. Genes Dev. 2010;24:2420-9 pubmed publisher..These effects are overridden by the Yap1 (Yes-associated protein 1) oncoprotein, which disrupts Lats2-ASPP1 binding and antagonizes the tumor-suppressing function of the Lats2/ASPP1/p53 axis. ..
- Schulten H, Al Maghrabi J, Al Ghamdi K, Salama S, Al Muhayawi S, Chaudhary A, et al. Mutational screening of RET, HRAS, KRAS, NRAS, BRAF, AKT1, and CTNNB1 in medullary thyroid carcinoma. Anticancer Res. 2011;31:4179-83 pubmed..The role of RAS mutations, in particular HRAS mutations, in sporadic RET-negative MTC has not been fully explored yet. Mutations in BRAF, AKT1, and CTNNB1 are likely not to play a role in MTC. ..
- Booth L, Roberts J, Poklepovic A, Kirkwood J, Sander C, Avogadri Connors F, et al. The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib. Cancer Biol Ther. 2018;19:132-137 pubmed publisher..Collectively, our data reinforce the concept that the irreversible ERBB1/2/4 inhibitor neratinib has the potential for use in the treatment of tumors expressing mutant RAS proteins. ..
- Dougherty M, Muller J, Ritt D, Zhou M, Zhou X, Copeland T, et al. Regulation of Raf-1 by direct feedback phosphorylation. Mol Cell. 2005;17:215-24 pubmed..These findings elucidate a critical Raf-1 regulatory mechanism that contributes to the sensitive, temporal modulation of Ras signaling. ..