Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3β

Li Ke Qu, Shirley Huang, Dionissios Baltzis, Ana Maria Rivas-Estilla, Olivier Pluquet, Maria Hatzoglou, Costas Koumenis, Yoichi Taya, Akihiko Yoshimura, Antonis E. Koromilas

研究成果: Article査読

214 被引用数 (Scopus)

抄録

The tumor suppressor p53, a sensor of multiple forms of cellular stress, is regulated by post-translational mechanisms to induce cell-cycle arrest, senescence, or apoptosis. We demonstrate that endoplasmic reticulum (ER) stress inhibits p53-mediated apoptosis. The mechanism of inhibition involves the increased cytoplasmic localization of p53 due to phosphorylation at serine 315 and serine 376, which is mediated by glycogen synthase kinase-3 β (GSK-3β). ER stress induces GSK-3β binding to p53 in the nucleus and enhances the cytoplasmic localization of the tumor suppressor. Inhibition of apoptosis caused by ER stress requires GSK-3β and does not occur in cells expressing p53 with mutation(s) of serine 315 and/or serine 376 to alanine(s). As a result of the increased cytoplasmic localization, ER stress prevents p53 stabilization and p53-mediated apoptosis upon DNA damage. It is concluded that inactivation of p53 is a protective mechanism utilized by cells to adapt to ER stress.

本文言語English
ページ(範囲)261-277
ページ数17
ジャーナルGenes and Development
18
3
DOI
出版ステータスPublished - 2004 2 1
外部発表はい

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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