Millán, OlgaBallester, AliciaCastrillo, AntonioOliva-Martinez, Jose LuisTravés, Paqui GRojas-Cabañeros, Jose MariaBoscá, Lisardo2025-01-232025-01-232003-01-30Millán O, Ballester A, Castrillo A, Oliva JL, Través PG, Rojas JM, Boscá L. H-Ras-specific activation of NF-kappaB protects NIH 3T3 cells against stimulus-dependent apoptosis. Oncogene. 2003 Jan 30;22(4):477-83.0950-9232https://hdl.handle.net/20.500.12105/26113Ras signaling involves the activation of several downstream pathways that exhibit isoform specificity. In this study, the basal and tumor necrosis factor alpha (TNFalpha)-induced activation of NF-kappaB has been examined in cells overexpressing H-Ras, K-Ras or N-Ras. Cells expressing H-Ras exhibited a basal kappaB activity that correlated with sustained IkappaB kinase activation and lower steady-state levels of IkappaBalpha in the cytosol. Upon activation with TNFalpha, the cells expressing the distinct Ras isoforms behaved similarly in terms of binding of nuclear proteins to a kappaB sequence and induction of a kappaB-dependent reporter gene. The basal activation of NF-kappaB in cells expressing H-Ras impaired staurosporine-induced apoptosis in these cells, through a mechanism that was NF-kappaB-dependent and inhibitable in the presence of z-VAD. Moreover, titration of caspase activation in response to staurosporine showed a significant resistance in cells expressing H-Ras when compared with the void vector or the N-Ras counterparts. These results indicate that the distinct Ras proteins have specific effects on the NF-kappaB pathway and that this action contributes to protect cells against apoptosis.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/RasSurvivalNuclear factorApoptosisTNFalphaStaurosporine3T3 CellsAnimalsApoptosisBase SequenceBlotting, WesternDNA PrimersElectrophoretic Mobility Shift AssayMiceNF-kappa BOncogene Protein p21(ras)PlasmidsTumor Necrosis Factor-alphaAttribution-NonCommercial-NoDerivatives 4.0 International12555061224477-48310.1038/sj.onc.12061791476-5594Oncogeneopen access