p19^ras Accelerates p73β‐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 p73β 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 and p73β accelerated p73β‐induced apoptosis through a caspase‐3 dependent pathway. Treatment with DEVD‐CHO, a caspase inhibitor, also strengthened p73β‐mediated apoptosis through a caspase‐3 dependent pathway. Furthermore, the enhanced transcriptional activity of endogenous p73β 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.

Keywords:

• p19^ras
• p73β
• caspase‐3
• apoptosis

Notes

These authors contributed equally to this work.

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