Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation

Cancer Cell. 2010 Aug 9;18(2):122-34. doi: 10.1016/j.ccr.2010.05.027.

Abstract

Che-1 is a RNA polymerase II binding protein involved in the regulation of gene transcription and, in response to DNA damage, promotes p53 transcription. In this study, we investigated whether Che-1 regulates mutant p53 expression. We found that Che-1 is required for sustaining mutant p53 expression in several cancer cell lines, and that Che-1 depletion by siRNA induces apoptosis both in vitro and in vivo. Notably, loss of Che-1 activates DNA damage checkpoint response and induces transactivation of p73. Therefore, these findings underline the important role that Che-1 has in survival of cells expressing mutant p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / physiology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / physiology*
  • DNA Damage*
  • DNA Repair / physiology
  • DNA-Binding Proteins / genetics
  • Humans
  • Mice
  • Nuclear Proteins / genetics
  • RNA, Small Interfering
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Transcription, Genetic / physiology*
  • Transplantation, Heterologous
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Proteins / genetics

Substances

  • AATF protein, human
  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • Repressor Proteins
  • TP73 protein, human
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins

Associated data

  • GEO/GSE20622