부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejcb.2006.10.004 Byline: Chun Shik Park, Mi Su Lee, Hye-jin Oh, Kyu Yeong Choi, Myeong Gu Yeo, Jang-soo Chun, Woo Keun Song Keywords: [beta]-Catenin; Cyclin-dependent kinase 6; Cyclin D1; Phosphorylation; Degradation; Wnt Abstract: [beta]-Catenin is implicated in quite different cellular processes, which require a fine-tuned regulation of its function. Here we demonstrate that cyclin-dependent kinase 6 (CDK6), in association with cyclin D1 (CCND1), directly binds to [beta]-catenin. We showed that CCND1-CDK6 phosphorylates [beta]-catenin on serine 45 (S45). This phosphorylation creates a priming site for glycogen synthase kinase 3[beta] (GSK3[beta]) and is both necessary and sufficient to initiate the [beta]-catenin phosphorylation-degradation cascade. Moreover, co-immunoprecipitation assays using Wnt3a-conditioned medium reveals that while Wnt stimulation leads to the dissociation of [beta]-catenin from axin and casein kinase I[alpha] (CKI[alpha]), Wnt treatment promotes an increase in CCND1 level and the association of [beta]-catenin with CCND1-CDK6. Furthermore, Wnt3a-stimulated cytosolic [beta]-catenin levels were higher in CDK6 knockout mouse embryonic fibroblasts (CDK6.sup.-/- MEFs) compared to wild-type MEFs. Thus, the CCND1-CDK6 complex is like to negatively regulate Wnt signaling by mediating [beta]-catenin phosphorylation and its subsequent degradation in Wnt-stimulated cells. Author Affiliation: Department of Life Science and Molecular Disease Research Center, Gwangju Institute of Science and Technology, 1 Oryong-dong, Buk-gu, Gwangju 500-712, Korea Article History: Received 28 July 2006; Revised 2 October 2006; Accepted 12 October 2006