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oai:repisalud.isciii.es:20.500.12105/261132025-12-18T12:56:21Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Millán, Olga author Ballester, Alicia author Castrillo, Antonio author Oliva-Martinez, Jose Luis author Través, Paqui G author Rojas-Cabañeros, Jose Maria author Boscá, Lisardo author 2003-01-30 Ras 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. Millán 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. 0950-9232 https://hdl.handle.net/20.500.12105/26113 12555061 10.1038/sj.onc.1206179 1476-5594 Oncogene Ras Survival Nuclear factor Apoptosis TNFalpha Staurosporine H-Ras-specific activation of NF-kappaB protects NIH 3T3 cells against stimulus-dependent apoptosis