p19(ras) Accelerates p73 beta-mediated Apoptosis through a Caspase-3 Dependent Pathway

Abstract

p19(ras) is an alternative splicing variant of the proto-oncogene c-H-ras pre-mRNA of p21(ras). In contrast to p21(ras), p19(ras) does not have a C-terminal CAAX motif that targets the plasma membrane and is localized to both the cytoplasm and nucleus. We found that p19(ras) activated the transcriptional activity of p73 beta through protein-protein interactions in the nucleus. p73 is known to play an important role in cellular damage responses such as apoptosis. Although p73 is a structural and functional homologue of p53, p73-mediated apoptosis has not yet been clearly elucidated. In this study, we demonstrate that the interaction between p19(ras) Tas and p73 beta accelerated p73 beta-induced apoptosis through a caspase-3 dependent pathway. Treatment with DEVD-CHO, a caspase inhibitor, also strengthened p73 beta-mediated apoptosis through a caspase-3 dependent pathway. Furthermore, the enhanced transcriptional activity of endogenous p73 beta by treatment with Taxol was amplified by p19(ras)-overexpression, which markedly increased caspase-3 dependent apoptosis in the p53-null SAOS2 cancer cell line. Our findings indicate a functional linkage between p19(ras) and p73 in caspase-3 mediated apoptosis of cancer cells.