p19ras amplifies p73β-induced apoptosis through mitochondrial pathway

p73 and p53 have been known to play an important role in cellular damage responses such as apoptosis. Although p73 is a structural and functional homolog of p53 tumor suppressor gene, much less is known about the mechanism of p73-induced apoptotic cell death. In this study, we demonstrate that p19ras interaction with p73β amplifies p73β-induced apoptotic signaling responses including Bax mitochondrial translocation, cytochrome c release, increased production of reactive oxygen species (ROS) and loss of mitochondrial transmembrane potential (ΔΨm). Furthermore, endogenous expression of p19ras and p73β is significantly increased by Taxol treatment, and Taxol-enhanced endogenous p73β transcriptional activities are further amplified by p19ras, which markedly increased cellular apoptosis in p53-null SAOS2 cancer cell line. These results have important implications for understanding the molecular events of p19ras to p73 functions in cancer cells.