文章基本信息

标题：Direct, activating interaction between glycogen synthase kinase-3β and p53 after DNA damage
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作者：Piyajit Watcharasit ; Gautam N. Bijur ; Jaroslaw W. Zmijewski 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：12
页码：7951-7955
DOI：10.1073/pnas.122062299
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Glycogen synthase kinase-3{beta} (GSK3{beta}) 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 GSK3{beta}. DNA damage induced by camptothecin, which activates the tumor suppressor p53, was found to activate GSK3{beta}. This activation occurred by a phosphorylation-independent mechanism involving direct binding of GSK3{beta} to p53, which was confined to the nucleus where p53 is localized, and mutated p53 (R175H) bound but did not activate GSK3{beta}. 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 GSK3{beta