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 language | English |
|---|---|
| Pages (from-to) | 7951-7955 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 99 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 11 2002 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Direct, activating interaction between glycogen synthase kinase-3β and p53 after DNA damage
AU - Watcharasit, Piyajit
AU - Bijur, Gautam N.
AU - Zmijewski, Jaroslaw W.
AU - Song, Ling
AU - Zmijewska, Anna
AU - Chen, Xinbin
AU - Johnson, Gail V W
AU - Jope, Richard S
PY - 2002/6/11
Y1 - 2002/6/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037062403&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037062403&partnerID=8YFLogxK
U2 - 10.1073/pnas.122062299
DO - 10.1073/pnas.122062299
M3 - Article
C2 - 12048243
AN - SCOPUS:0037062403
VL - 99
SP - 7951
EP - 7955
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 12
ER -