p53 Retards cell-growth and suppresses etoposide-induced apoptosis in Pin1-deficient mouse embryonic fibroblasts

Biochem Biophys Res Commun. 2012 May 25;422(1):133-8. doi: 10.1016/j.bbrc.2012.04.121. Epub 2012 Apr 30.

Abstract

We studied the effects of Pin1, a regulatory molecule of the oncosuppressor p53, on both cell cycle arrest and apoptosis by treating primary mouse embryonic fibroblasts (MEFs) with etoposide. Etoposide induced G1 arrest in both wild-type and Pin1 null (pin1(-/-)) MEFs, and G2/M arrest and apoptotic cell death in MEFs lacking either p53 only (p53(-/-)) or both Pin1 and p53 (pin1(-/-)p53(-/-)). Both pin1(-/-) and pin1(-/-)p53(-/-) MEFs were enhanced the release of cytochrome c from the mitochondria, which might induce apoptosis. In response to etoposide treatment, apoptotic cell death was displayed in pin1(-/-)p53(-/-) MEFs but not in pin1(-/-) MEFs. These results suggest that p53 retards growth and suppresses etoposide-induced apoptosis in pin1(-/-) MEFs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Cell Proliferation*
  • Cells, Cultured
  • Embryo, Mammalian / cytology
  • Etoposide / pharmacology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / physiology
  • G1 Phase Cell Cycle Checkpoints
  • Mice
  • Mitochondria / metabolism
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Permeability
  • Phosphorylation
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • NIMA-Interacting Peptidylprolyl Isomerase
  • Tumor Suppressor Protein p53
  • Etoposide
  • Peptidylprolyl Isomerase
  • Pin1 protein, mouse