Inhibition of Ras oncogenic activity by Ras protooncogenes

International Journal of Cancer. Journal International Du Cancer
Roberto DiazAngel Pellicer

Abstract

Point mutations in ras genes have been found in a large number and wide variety of human tumors. These oncogenic Ras mutants are locked in an active GTP-bound state that leads to a constitutive and deregulated activation of Ras function. The dogma that ras oncogenes are dominant, whereby the mutation of a single allele in a cell will predispose the host cell to transformation regardless of the presence of the normal allele, is being challenged. We have seen that increasing amounts of Ras protooncogenes are able to inhibit the activity of the N-Ras oncogene in the activation of Elk in NIH 3T3 cells and in the formation of foci. We have been able to determine that the inhibitory effect is by competition between Ras protooncogenes and the N-Ras oncogene that occurs first at the effector level at the membranes, then at the processing level and lastly at the effector level in the cytosol. In addition, coexpression of the N-Ras protooncogene in thymic lymphomas induced by the N-Ras oncogene is associated with increased levels of p107, p130 and cyclin A and decreased levels of Rb. In the present report, we have shown that the N-Ras oncogene is not truly dominant over Ras protooncogenes and their competing activities might be depending...Continue Reading

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Citations

Aug 3, 2011·Journal of Cellular Physiology·Marta BenetAngel Pellicer
Dec 21, 2013·International Journal of Experimental Pathology·Feijun LuoMark J Arends
Mar 19, 2013·The Biochemical Journal·Carolyn BentleyDavid Stokoe
Apr 12, 2013·International Journal of Molecular Sciences·Michael P HunterJohn P O'Bryan
Apr 25, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chen-Hsiang YeangArnold Levine
May 1, 2021·Genes·Erin Sheffels, Robert L Kortum
Apr 26, 2011·Current Biology : CB·James N HigginbothamRobert J Coffey

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