Glycogen synthase kinase 3β phosphorylates p21WAF1/CIP1 for proteasomal degradation after UV irradiation

Young Lee Ji, Jin Yu Su, Yun Gyu Park, Joon Kim, Jeongwon Sohn

Research output: Contribution to journalArticle

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Abstract

UV irradiation has been reported to induce p21WAF1/CIP1 protein degradation through a ubiquitin-proteasome pathway, but the underlying biochemical mechanism remains to be elucidated. Here, we show that ser-114 phosphorylation of p21 protein by glycogen synthase ldnase 3β (GSK-3β) is required for its degradation in response to UV irradiation and that GSK-3β activation is a downstream event in the ATR signaling pathway triggered by UV. UV transiently increased GSK-3β activity, and this increase could be blocked by caffeine or by ATR small interfering RNA, indicating ATR-dependent activation of GSK-3β. ser-114, located within the putative GSK-3β target sequence, was phosphorylated by GSK-3β upon UV exposure. The nonphosphorylatable S114A mutant of p21 was protected from UV-induced destabilization. Degradation of p21 protein by UV irradiation was independent of p53 status and prevented by proteasome inhibitors. In contrast to the previous report, the proteasomal degradation of p21 appeared to be ubiquitination independent. These data show that GSK-3β is activated by UV irradiation through the ATR signaling pathway and phosphorylates p21 at ser-114 for its degradation by the proteasome. To our knowledge, this is the first demonstration of GSK-3β as the missing link between UV-induced ATR activation and p21 degradation.

Original languageEnglish
Pages (from-to)3187-3198
Number of pages12
JournalMolecular and Cellular Biology
Volume27
Issue number8
DOIs
Publication statusPublished - 2007 Apr 1

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Glycogen Synthase Kinase 3
Proteasome Endopeptidase Complex
Proteolysis
Glycogen Synthase
Proteasome Inhibitors
Ubiquitination
Ubiquitin
Caffeine
Small Interfering RNA
Phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Glycogen synthase kinase 3β phosphorylates p21WAF1/CIP1 for proteasomal degradation after UV irradiation. / Ji, Young Lee; Su, Jin Yu; Park, Yun Gyu; Kim, Joon; Sohn, Jeongwon.

In: Molecular and Cellular Biology, Vol. 27, No. 8, 01.04.2007, p. 3187-3198.

Research output: Contribution to journalArticle

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