Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage.
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.
Watcharasit
Piyajit
P
Departments of Psychiatry and Behavioral Neurobiology and Cell Biology, University of Alabama, Birmingham, AL 35294-0017, USA.
Bijur
Gautam N
GN
Zmijewski
Jaroslaw W
JW
Song
Ling
L
Zmijewska
Anna
A
Chen
Xinbin
X
Johnson
Gail V W
GV
Jope
Richard S
RS
D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002166:Camptothecin / Q000494:pharmacology; D002467:Cell Nucleus / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004249:DNA Damage; D017931:DNA Primers; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D007700:Kinetics; D009447:Neuroblastoma; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D002166:Camptothecin