Direct, activating interaction between glycogen synthase kinase-3β and p53 after DNA damage

Piyajit Watcharasit, Gautam N. Bijur, Jaroslaw W. Zmijewski, Ling Song, Anna Zmijewska, Xinbin Chen, Gail V W Johnson, Richard S Jope

Research output: Contribution to journalArticle

216 Citations (Scopus)

Abstract

Glycogen synthase kinase-3β (GSK3β) is a central figure in Wnt signaling, in which its activity is controlled by regulatory binding proteins. Here we show that binding proteins outside the Wnt pathway also control the activity of GSK3β. DNA damage induced by camptothecin, which activates the tumor suppressor p53, was found to activate GSK3β. This activation occurred by a phosphorylation-independent mechanism involving direct binding of GSK3β to p53, which was confined to the nucleus where p53 is localized, and mutated p53 (R175H) bound but did not activate GSK3β. Activation of GSK3 promoted responses to p53 including increases in p21 levels and caspase-3 activity. Thus, after DNA damage there is a direct interaction between p53 and GSK3β, and these proteins act in concert to regulate cellular responses to DNA damage.

Original languageEnglish
Pages (from-to)7951-7955
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number12
DOIs
StatePublished - Jun 11 2002
Externally publishedYes

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Glycogen Synthase Kinase 3
DNA Damage
Carrier Proteins
Camptothecin
Wnt Signaling Pathway
Caspase 3
Phosphorylation

ASJC Scopus subject areas

  • Genetics
  • General

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Direct, activating interaction between glycogen synthase kinase-3β and p53 after DNA damage. / Watcharasit, Piyajit; Bijur, Gautam N.; Zmijewski, Jaroslaw W.; Song, Ling; Zmijewska, Anna; Chen, Xinbin; Johnson, Gail V W; Jope, Richard S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 12, 11.06.2002, p. 7951-7955.

Research output: Contribution to journalArticle

Watcharasit, Piyajit ; Bijur, Gautam N. ; Zmijewski, Jaroslaw W. ; Song, Ling ; Zmijewska, Anna ; Chen, Xinbin ; Johnson, Gail V W ; Jope, Richard S. / Direct, activating interaction between glycogen synthase kinase-3β and p53 after DNA damage. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 12. pp. 7951-7955.
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