Glycogen synthase kinase-3beta (GSK3beta) 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 GSK3beta. DNA damage induced by camptothecin, which activates the tumor suppressor p53, was found to activate GSK3beta. This activation occurred by a phosphorylation-independent mechanism involving direct binding of GSK3beta to p53, which was confined to the nucleus where p53 is localized, and mutated p53 (R175H) bound but did not activate GSK3beta. 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 GSK3beta, and these proteins act in concert to regulate cellular responses to DNA damage.
We have not found any resources mentioned in this publication.
SciCrunch® is a data sharing and display platform. Anyone can create a custom portal where they can select searchable subsets of hundreds of data sources, brand their web pages and create their community. SciCrunch® will push data updates automatically to all portals on a weekly basis. User communities can also add their own data to SciCrunch®, however this is not currently a free service.