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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
MeSH Review

Genes, ras

 
 
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Disease relevance of Genes, ras

  • The first, a benign hyperplasia of the Harderian lacrimal gland, is diffuse, involves the entire gland, and likely requires only the abnormal action of the v-Ha-ras gene [1].
  • Loss of ras oncogene mutation in a myelodysplastic syndrome after low-dose cytarabine therapy [2].
  • A combination of DNA hybridization analyses and tissue sectioning techniques demonstrate that ras gene mutations occur in over a third of human colorectal cancers, that most of the mutations are at codon 12 of the c-Ki-ras gene and that the mutations usually precede the development of malignancy [3].
  • Over 90% of tumours, including premalignant papillomas, initiated with dimethylbenzanthracene (DMBA) have a specific A----T transversion at the second nucleotide of codon 61 of the Harvey-ras (Ha-ras) gene [4].
  • We have now used monoclonal antibodies directed against a synthetic peptide reflecting sequences of the human T24 ras gene product to define ras p21 protein expression in a spectrum of colonic disease states [5].
 

Psychiatry related information on Genes, ras

 

High impact information on Genes, ras

  • The 3'UTRs of the human RAS genes contain multiple LCSs, allowing let-7 to regulate RAS expression. let-7 expression is lower in lung tumors than in normal lung tissue, while RAS protein is significantly higher in lung tumors, providing a possible mechanism for let-7 in cancer [7].
  • By screening for mutations that suppress the vulval defects caused by a constitutively active let-60 ras gene, we identified six loss-of-function alleles of ksr-1, a novel C. elegans gene [8].
  • Using a reconstituted mouse prostate organ, the effects on endogenous p53 expression of the ras oncogene or of the ras + myc oncogenes were investigated [9].
  • The rap1/Krev-1 gene encodes a ras-related protein that suppresses transformation by ras oncogenes [10].
  • For example, the human H-ras gene can substitute for yeast RAS; the relationship is sufficiently close that dominant Ha-ras mutations that inhibit CDC25 have been found (Powers et al., 1989) [11].
 

Chemical compound and disease context of Genes, ras

 

Biological context of Genes, ras

  • This evidence suggests that NF1 encodes a cytoplasmic GAP-like protein that may be involved in the control of cell growth by interacting with proteins such as the RAS gene product [17].
  • Recent studies have demonstrated that the cellular tumour antigen p53 (ref. 1) can complement activated ras genes in the transformation of rat fibroblasts, suggesting that the gene encoding p53 may act as an oncogene [18].
  • Transfection studies show that the p53 gene, in collaboration with the activated ras oncogene, can transform cells [19].
  • Harvey (Ha-MSV) and Kirsten (Ki-MSV) murine sarcoma viruses induce tumours in animals and transform various cells in culture because of the expression of the ras oncogene product, p21 (ref. 1). Proto-oncogenes homologous with these genes are highly conserved evolutionarily and activated ras oncogenes have been detected in many human cancers [20].
  • We propose that recA protein may change its conformation upon ATP hydrolysis in a manner analogous to one such protein, the p21 protein from the ras oncogene [21].
 

Anatomical context of Genes, ras

 

Associations of Genes, ras with chemical compounds

  • These results indicate that structural mutations which activate ras gene transforming activity do not alter the protein's known biochemical parameters and in particular do not affect the protein's intrinsic ability to bind guanine nucleotides [27].
  • Vulval differentiation in Caenorhabditis elegans is controlled by intercellular signalling mediated by a receptor tyrosine kinase and a ras gene product [28].
  • We demonstrate a reproducible increase in 1,2-diacylglycerol, in the absence of a detectable increase in inositol phosphates, in transformed cells containing Ha-ras oncogenes and with different membrane targeting signals for the ras p21 protein [29].
  • One of the most commonly found transforming ras oncogenes in human tumours has a valine codon replacing the glycine codon at position 12 of the normal c-Ha-ras gene [30].
  • Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene [29].
 

Gene context of Genes, ras

  • In these experiments we demonstrate that purified RAS proteins, whether derived from the yeast RAS1 or RAS2 or the human H-ras genes, activate yeast adenylate cyclase in the presence of guanine nucleotides [31].
  • We have cloned the let-60 gene, and shown that it encodes a gene product identical in 84% of its first 164 amino acids to ras gene products from other vertebrate and invertebrate species [32].
  • We have identified a gene, SRV2, mutations of which alleviate stress sensitivity in strains carrying an activated RAS gene [33].
  • The yeast Saccharomyces cerevisiae contains two functional homologues of the ras oncogene family, RAS1 and RAS2 [34].
  • Two C. elegans MAP kinase genes, mpk-1 and mpk-2 (mpk, MAP kinase), were cloned using degenerate oligonucleotide primers and PCR amplification; in parallel, genes involved in vulval induction were identified by screening for mutations that suppress the vulval defects caused by an activated let-60 ras gene [35].
 

Analytical, diagnostic and therapeutic context of Genes, ras

References

  1. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Sinn, E., Muller, W., Pattengale, P., Tepler, I., Wallace, R., Leder, P. Cell (1987) [Pubmed]
  2. Loss of ras oncogene mutation in a myelodysplastic syndrome after low-dose cytarabine therapy. Layton, D.M., Mufti, G.J., Lyons, J., Janssen, J.W., Bartram, C.R. N. Engl. J. Med. (1988) [Pubmed]
  3. Prevalence of ras gene mutations in human colorectal cancers. Bos, J.L., Fearon, E.R., Hamilton, S.R., Verlaan-de Vries, M., van Boom, J.H., van der Eb, A.J., Vogelstein, B. Nature (1987) [Pubmed]
  4. Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Quintanilla, M., Brown, K., Ramsden, M., Balmain, A. Nature (1986) [Pubmed]
  5. Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases. Thor, A., Horan Hand, P., Wunderlich, D., Caruso, A., Muraro, R., Schlom, J. Nature (1984) [Pubmed]
  6. The 'cerebral diabetes' paradigm for unipolar depression. Newman, J.C., Holden, R.J. Med. Hypotheses (1993) [Pubmed]
  7. RAS is regulated by the let-7 microRNA family. Johnson, S.M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K.L., Brown, D., Slack, F.J. Cell (2005) [Pubmed]
  8. The ksr-1 gene encodes a novel protein kinase involved in Ras-mediated signaling in C. elegans. Kornfeld, K., Hom, D.B., Horvitz, H.R. Cell (1995) [Pubmed]
  9. Ras-induced hyperplasia occurs with mutation of p53, but activated ras and myc together can induce carcinoma without p53 mutation. Lu, X., Park, S.H., Thompson, T.C., Lane, D.P. Cell (1992) [Pubmed]
  10. Molecular cloning of a GTPase activating protein specific for the Krev-1 protein p21rap1. Rubinfeld, B., Munemitsu, S., Clark, R., Conroy, L., Watt, K., Crosier, W.J., McCormick, F., Polakis, P. Cell (1991) [Pubmed]
  11. Dual regulation of meiosis in yeast. Malone, R.E. Cell (1990) [Pubmed]
  12. Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Fisher, G.H., Wellen, S.L., Klimstra, D., Lenczowski, J.M., Tichelaar, J.W., Lizak, M.J., Whitsett, J.A., Koretsky, A., Varmus, H.E. Genes Dev. (2001) [Pubmed]
  13. Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17 beta-estradiol or v-Ha-ras oncogene. Dickson, R.B., Kasid, A., Huff, K.K., Bates, S.E., Knabbe, C., Bronzert, D., Gelmann, E.P., Lippman, M.E. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  14. Cotransfection of granulosa cells with simian virus 40 and Ha-RAS oncogene generates stable lines capable of induced steroidogenesis. Amsterdam, A., Zauberman, A., Meir, G., Pinhasi-Kimhi, O., Suh, B.S., Oren, M. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  15. Reduction in the frequency of activated ras oncogenes in rat mammary carcinomas with increasing N-methyl-N-nitrosourea doses or increasing prolactin levels. Zhang, R., Haag, J.D., Gould, M.N. Cancer Res. (1990) [Pubmed]
  16. Mutational activation of the cellular Harvey ras oncogene in rat esophageal papillomas induced by methylbenzylnitrosamine. Wang, Y., You, M., Reynolds, S.H., Stoner, G.D., Anderson, M.W. Cancer Res. (1990) [Pubmed]
  17. The neurofibromatosis type 1 gene encodes a protein related to GAP. Xu, G.F., O'Connell, P., Viskochil, D., Cawthon, R., Robertson, M., Culver, M., Dunn, D., Stevens, J., Gesteland, R., White, R. Cell (1990) [Pubmed]
  18. Translocation of the p53 gene in t(15;17) in acute promyelocytic leukaemia. Le Beau, M.M., Westbrook, C.A., Diaz, M.O., Rowley, J.D., Oren, M. Nature (1985) [Pubmed]
  19. Human p53 gene localized to short arm of chromosome 17. Miller, C., Mohandas, T., Wolf, D., Prokocimer, M., Rotter, V., Koeffler, H.P. Nature (1986) [Pubmed]
  20. The ras oncogene product p21 is not a regulatory component of adenylate cyclase. Beckner, S.K., Hattori, S., Shih, T.Y. Nature (1985) [Pubmed]
  21. Structure of the recA protein-ADP complex. Story, R.M., Steitz, T.A. Nature (1992) [Pubmed]
  22. v-erbA cooperates with sarcoma oncogenes in leukemic cell transformation. Kahn, P., Frykberg, L., Brady, C., Stanley, I., Beug, H., Vennström, B., Graf, T. Cell (1986) [Pubmed]
  23. Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1. Shimizu, K., Birnbaum, D., Ruley, M.A., Fasano, O., Suard, Y., Edlund, L., Taparowsky, E., Goldfarb, M., Wigler, M. Nature (1983) [Pubmed]
  24. Biological properties of human c-Ha-ras1 genes mutated at codon 12. Seeburg, P.H., Colby, W.W., Capon, D.J., Goeddel, D.V., Levinson, A.D. Nature (1984) [Pubmed]
  25. Caenorhabditis elegans ras gene let-60 acts as a switch in the pathway of vulval induction. Beitel, G.J., Clark, S.G., Horvitz, H.R. Nature (1990) [Pubmed]
  26. ras Oncogene p21 expression is increased in premalignant lesions and high grade bladder carcinoma. Viola, M.V., Fromowitz, F., Oravez, S., Deb, S., Schlom, J. J. Exp. Med. (1985) [Pubmed]
  27. Activation of ras genes in human tumors does not affect localization, modification, or nucleotide binding properties of p21. Finkel, T., Der, C.J., Cooper, G.M. Cell (1984) [Pubmed]
  28. C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation. Han, M., Golden, A., Han, Y., Sternberg, P.W. Nature (1993) [Pubmed]
  29. Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene. Lacal, J.C., Moscat, J., Aaronson, S.A. Nature (1987) [Pubmed]
  30. Structural differences between a ras oncogene protein and the normal protein. Tong, L.A., de Vos, A.M., Milburn, M.V., Jancarik, J., Noguchi, S., Nishimura, S., Miura, K., Ohtsuka, E., Kim, S.H. Nature (1989) [Pubmed]
  31. Differential activation of yeast adenylate cyclase by wild-type and mutant RAS proteins. Broek, D., Samiy, N., Fasano, O., Fujiyama, A., Tamanoi, F., Northup, J., Wigler, M. Cell (1985) [Pubmed]
  32. let-60, a gene that specifies cell fates during C. elegans vulval induction, encodes a ras protein. Han, M., Sternberg, P.W. Cell (1990) [Pubmed]
  33. SRV2, a gene required for RAS activation of adenylate cyclase in yeast. Fedor-Chaiken, M., Deschenes, R.J., Broach, J.R. Cell (1990) [Pubmed]
  34. CDC25: a component of the RAS-adenylate cyclase pathway in Saccharomyces cerevisiae. Robinson, L.C., Gibbs, J.B., Marshall, M.S., Sigal, I.S., Tatchell, K. Science (1987) [Pubmed]
  35. A MAP kinase homolog, mpk-1, is involved in ras-mediated induction of vulval cell fates in Caenorhabditis elegans. Lackner, M.R., Kornfeld, K., Miller, L.M., Horvitz, H.R., Kim, S.K. Genes Dev. (1994) [Pubmed]
  36. v-rasH induces non-small cell phenotype, with associated growth factors and receptors, in a small cell lung cancer cell line. Falco, J.P., Baylin, S.B., Lupu, R., Borges, M., Nelkin, B.D., Jasti, R.K., Davidson, N.E., Mabry, M. J. Clin. Invest. (1990) [Pubmed]
  37. Nerve growth factor acts through cAMP-dependent protein kinase to increase the number of sodium channels in PC12 cells. Kalman, D., Wong, B., Horvai, A.E., Cline, M.J., O'Lague, P.H. Neuron (1990) [Pubmed]
  38. Sequential protooncogene expression during regeneration in rat stomach. Ito, T., Hayashi, N., Sasaki, Y., Morita, Y., Kawano, S., Fusamoto, H., Sato, N., Tohyama, M., Kamada, T. Gastroenterology (1990) [Pubmed]
  39. Immunological evidence for the association of p53 with a heat shock protein, hsc70, in p53-plus-ras-transformed cell lines. Hinds, P.W., Finlay, C.A., Frey, A.B., Levine, A.J. Mol. Cell. Biol. (1987) [Pubmed]
  40. Cellular ras oncogene expression and cell cycle measured by flow cytometry in hematopoietic cell lines. Andreeff, M., Slater, D.E., Bressler, J., Furth, M.E. Blood (1986) [Pubmed]
 
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