國家衛生研究院 NHRI:Item 3990099045/8580
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    题名: CDK2 phosphorylation regulates the protein stability of KLF10 by interfering with binding of the E3 ligase SIAH1
    作者: Lin, CH;Lin, SY;Chang, HW;Ko, LJ;Tseng, YS;Chang, VHS;Yu, WCY
    贡献者: National Institute of Cancer Research
    摘要: Downregulation of multiple cell cycle-regulatory molecules is a dominant event in TGF-β1-mediated growth inhibition of human carcinoma cells. It is known that KLF10 mimics the anti-proliferative and apoptotic effects that TGF-β1 has on epithelial cell growth and the growth of various tumor cells; based on these findings it is considered as a tumor suppressor. KLF10 protein expression is tightly associated with cell cycle-dependent events. However, the regulatory mechanism and its biological meaning have not been identified. In this study, we have demonstrated that KLF10 is a substrate of CDK2/cyclin E and can be phosphorylated. We also have shown that KLF10 efficiently binds to CDK2, while binding much less to CDK4, and displaying no binding to Cdk6. Using mass spectrometry, site direct mutagenesis, in vitro kinase assays and depletion assays, we have established that CDK2 phosphorylates Ser-206, which subsequently affects the steady state level of KLF10 in cells. Our studies have also proved that CDK2 up-regulates the protein level of KLF10 through reducing its association with SIAH1, a KLF10 E3-ubiqutin ligase involved in proteasomal degradation. Taken all together, these findings indicate that CDK2-dependent phosphorylation regulates KLF10 stability and that this affects the role of KLF10 in cell.
    日期: 2015-05
    關聯: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2015 May;1853(5):1174-1181.
    Link to: http://dx.doi.org/10.1016/j.bbamcr.2015.02.018
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0167-4889&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000353176700027
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84924150032
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