國家衛生研究院 NHRI:Item 3990099045/4313
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    題名: Pro-apoptotic role of Cdc25A: Activation of cyclin B1/Cdc2 by the Cdc25A C-terminal domain
    作者: Chou, ST;Yen, YC;Lee, CM;Chen, MS
    貢獻者: National Institute of Cancer Research
    摘要: Cdc25A is a dual-specificity protein phosphatase that activates Cyclin/Cyclin-dependent protein kinase (Cdk) complexes by removing inhibitory phosphates from conserved threonine and tyrosine in Cdks. To address how Cdc25A promotes apoptosis, Jurkat cells were treated with staurosporine, an apoptosis inducer. Upon staurosporine treatment, a Cdc25A C-terminal 37-kD fragment, designated C37, was generated by caspase cleavage at D223. T507 in C37 became dephosphorylated, which prevented 14-3-3 binding, as shown previously. C37 exhibited higher phosphatase activity than full-length Cdc25A. C37 with alanine substitution for T507 (C37/T507A) that imitated the cleavage product during staurosporine treatment interacted with Cdc2, Cdk2, Cyclin A, and Cyclin B1, and markedly activated Cyclin B1/Cdc2. The dephosphorylation of T507 might expose the Cdc2/Cdk2 docking site in C37. C37/T507A also induced apoptosis in Jurkat and K562 cells, resulting from activating Cyclin B1/Cdc2, but not Cdk2. Thus, this study reveals that Cdc25A is a pro-apoptotic protein that amplifies staurosporine-induced apoptosis through the activation of Cyclin B1/Cdc2 by its C-terminal domain.
    日期: 2010-06-04
    關聯: Journal of Biological Chemistry. 2010 Jun;285(23):17833-17845.
    Link to: http://dx.doi.org/10.1074/jbc.M109.078386
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000278133400061
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77952949714
    顯示於類別:[陳美霞(2002-2009)] 期刊論文

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