This Article Full Text Full Text (PDF) Supplemental material Other Versions of this Article: MCB.01461-06v1 27/8/3187    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, J. Y. Articles by Sohn, J. Search for Related Content PubMed PubMed Citation Articles by Lee, J. Y. Articles by Sohn, J.

Glycogen Synthase Kinase 3ß Phosphorylates p21^WAF1/CIP1 for Proteasomal Degradation after UV Irradiation ^,

Department of Biochemistry, Korea University College of Medicine, Seoul 136-705, South Korea,¹ School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea,² Korean Institute of Molecular Medicine and Nutrition, Seoul 136-705, South Korea³

Received 8 August 2006/ Returned for modification 4 September 2006/ Accepted 23 January 2007

UV irradiation has been reported to induce p21^WAF1/CIP1 protein degradation through a ubiquitin-proteasome pathway, but the underlying biochemical mechanism remains to be elucidated. Here, we show that ser-114 phosphorylation of p21 protein by glycogen synthase kinase 3ß (GSK-3ß) is required for its degradation in response to UV irradiation and that GSK-3ß activation is a downstream event in the ATR signaling pathway triggered by UV. UV transiently increased GSK-3ß activity, and this increase could be blocked by caffeine or by ATR small interfering RNA, indicating ATR-dependent activation of GSK-3ß. ser-114, located within the putative GSK-3ß target sequence, was phosphorylated by GSK-3ß upon UV exposure. The nonphosphorylatable S114A mutant of p21 was protected from UV-induced destabilization. Degradation of p21 protein by UV irradiation was independent of p53 status and prevented by proteasome inhibitors. In contrast to the previous report, the proteasomal degradation of p21 appeared to be ubiquitination independent. These data show that GSK-3ß is activated by UV irradiation through the ATR signaling pathway and phosphorylates p21 at ser-114 for its degradation by the proteasome. To our knowledge, this is the first demonstration of GSK-3ß as the missing link between UV-induced ATR activation and p21 degradation.

Published ahead of print on 5 February 2007.

Supplemental material for this article may be found at http://mcb.asm.org/.

This article has been cited by other articles:

• Zhou, F., Zhang, L., Wang, A., Song, B., Gong, K., Zhang, L., Hu, M., Zhang, X., Zhao, N., Gong, Y. (2008). The Association of GSK3{beta} with E2F1 Facilitates Nerve Growth Factor-induced Neural Cell Differentiation. J. Biol. Chem. 283: 14506-14515 [Abstract] [Full Text]  
• Plotnikov, A., Li, Y., Tran, T. H., Tang, W., Palazzo, J. P., Rui, H., Fuchs, S. Y. (2008). Oncogene-Mediated Inhibition of Glycogen Synthase Kinase 3{beta} Impairs Degradation of Prolactin Receptor. Cancer Res. 68: 1354-1361 [Abstract] [Full Text]  
• Jin, Y., Zeng, S. X., Sun, X.-X., Lee, H., Blattner, C., Xiao, Z., Lu, H. (2008). MDMX Promotes Proteasomal Turnover of p21 at G1 and Early S Phases Independently of, but in Cooperation with, MDM2. Mol. Cell. Biol. 28: 1218-1229 [Abstract] [Full Text]