Roles of Akt and glycogen synthase kinase 3beta in the ultraviolet B induction of cyclooxygenase-2 transcription in human keratinocytes.
Ultraviolet B (UVB)-induced cyclooxygenase-2 ( COX-2) expression plays an important role in UVB tumor promotion. We examined whether Akt and glycogen synthase kinase 3beta (GSK-3beta), components of the phosphatidylinositol 3'-kinase pathway, are involved in UVB induction of COX-2 transcription. UVB caused Akt phosphorylation at both Thr-308 and Ser-473 that was inhibited by LY294002, a phosphatidylinositol 3'-kinase inhibitor. LY294002 also decreased the expression of endogenous COX-2 protein and a luciferase construct driven by COX-2 promoter. Similarly, UVB caused phosphorylation of GSK-3beta (Ser-9) and presumably inactivation of GSK-3beta. Inhibition of GSK-3beta by lithium induced endogenous COX-2 protein expression and COX-2 promoter activity. Finally, overexpression of a dominant-negative Akt mutant or wild-type GSK-3beta suppressed UVB-mediated induction of COX-2 promoter. These studies suggest that inactivation of GSK-3beta through activation of Akt plays an important role in the UVB induction of COX-2 transcription.[1]References
- Roles of Akt and glycogen synthase kinase 3beta in the ultraviolet B induction of cyclooxygenase-2 transcription in human keratinocytes. Tang, Q., Gonzales, M., Inoue, H., Bowden, G.T. Cancer Res. (2001) [Pubmed]
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