p19(ras) amplifies p73beta-induced apoptosis through mitochondrial pathway

Biochem Biophys Res Commun. 2008 Aug 15;373(1):146-50. doi: 10.1016/j.bbrc.2008.06.010. Epub 2008 Jun 12.

Abstract

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 p19(ras) interaction with p73beta amplifies p73beta-induced apoptotic signaling responses including Bax mitochondrial translocation, cytochrome c release, increased production of reactive oxygen species (ROS) and loss of mitochondrial transmembrane potential (DeltaPsi(m)). Furthermore, endogenous expression of p19(ras) and p73beta is significantly increased by Taxol treatment, and Taxol-enhanced endogenous p73beta transcriptional activities are further amplified by p19(ras), which markedly increased cellular apoptosis in p53-null SAOS2 cancer cell line. These results have important implications for understanding the molecular events of p19(ras) to p73 functions in cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis*
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Membrane Potential, Mitochondrial
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Neoplasms / metabolism*
  • Nuclear Proteins / metabolism*
  • Paclitaxel / pharmacology
  • Protein Transport
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Reactive Oxygen Species / metabolism
  • Tumor Protein p73
  • Tumor Suppressor Proteins / metabolism*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Reactive Oxygen Species
  • TP73 protein, human
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein
  • Cytochromes c
  • Proto-Oncogene Proteins p21(ras)
  • Paclitaxel