國家衛生研究院 NHRI:Item 3990099045/2877
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    題名: Mitochondrial anchoring of PKC alpha by PICK1 confers resistance to etoposide-induced apoptosis
    作者: Wang, WL;Yeh, SF;Huang, EYK;Lu, YL;Wang, CF;Huang, CYF;Lin, WJ
    貢獻者: National Institute of Cancer Research
    摘要: Various pathways, including regulation of functions of the 136-2 family, are implicated in the survival promotion by PKC alpha, however the molecular mechanisms are still obscure. We have previously demonstrated that PKCa is selectively anchored to mitochondria by PICK I in fibroblasts NIH 3T3. In this study, we show that overexpression of PICK1 in leukemia REH confers resistance to etoposide-induced apoptosis, which requires an interaction with PKC alpha as the non-interacting mutant PICK1 loses the pro-survival activity. The PKC alpha selective inhibitor Go6976 also abolishes the anti-apoptotic effect indicating a requirement for PKC activity. Disruption of PICK1/PKC alpha interactions by inhibitory peptides significantly increases cellular susceptibility to etoposide. Similar effects are also observed in HL60 cells, which exhibit an intrinsic resistance to etoposide. Molecular analysis shows that the wild type PICK1, but not the non-interacting mutant, prevents the loss of mitochondrial membrane potential with a coincident increase in phosphorylation of the anti-apoptotic Bcl-2(Ser70) and a decrease in dimerization of the pro-apoptotic Bax. PICK1 may provide the spatial proximity for phosphorylation of Bcl-2(Ser70) by PKCa which then leads to a higher survival. Taken together, our results suggest that PICK1 may mediate the pro-survival activity of PKC alpha by serving as a molecular link between PKCa and mitochondria.
    關鍵詞: Biochemistry & Molecular Biology;Cell Biology
    日期: 2007-10
    關聯: Apoptosis. 2007 Oct;12(10):1857-1871.
    Link to: http://dx.doi.org/10.1007/s10495-007-0098-0
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1360-8185&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000249610700011
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34848834834
    顯示於類別:[黃奇英(2005-2007)] 期刊論文

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