p53-independent apoptosis is induced by the p19ARF tumor suppressor

Keitaro Tsuji, Kiyohisa Mizumoto, Haruka Sudo, Keisuke Kouyama, Etsuro Ogata, Masaaki Matsuoka

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

p19ARF is a potent tumor suppressor. By inactivating Mdm2, p19ARF upregulates p53 activities to induce cell cycle arrest and sensitize cells to apoptosis in the presence of collateral signals. It has also been demonstrated that cell cycle arrest is induced by overexpressed p19ARF in p53-deficient mouse embryonic fibroblasts, only in the absence of the Mdm2 gene. Here, we show that apoptosis can be induced without additional apoptosis signals by expression of p19ARF using an adenovirus-mediated expression system in p53-intact cell lines as well as p53-deficient cell lines. Also, in primary mouse embryonic fibroblasts (MEFs) lacking p53/ARF, p53-independent apoptosis is induced irrespective of Mdm2 status by expression of p19ARF. In agreement, p19ARF-mediated apoptosis in U2OS cells, but not in Saos2 cells, was attenuated by coexpression of Mdm2. We thus conclude that there is a p53-independent pathway for p19ARF-induced apoptosis that is insensitive to inhibition by Mdm2.

Original languageEnglish
Pages (from-to)621-629
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume295
Issue number3
DOIs
Publication statusPublished - 2002 Jan 1

Keywords

  • Apoptosis
  • Cell cycle arrest
  • Mdm2
  • p19
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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