國家衛生研究院 NHRI:Item 3990099045/8574
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    题名: Skp2-dependent ubiquitination and activation of LKB1 is essential for cancer cell survival under energy stress
    作者: Lee, SW;Li, CF;Jin, G;Cai, Z;Han, F;Chan, CH;Yang, WL;Li, BK;Rezaeian, Abdol?H;Li, HY;Huang, HY;Lin, HK
    贡献者: National Institute of Cancer Research
    摘要: Summary LKB1 is activated by forming a heterotrimeric complex with STRAD and MO25. Recent studies suggest that LKB1 has pro-oncogenic functions, besides acting as a tumor suppressor. How the LKB1 activity is maintained and how LKB1 regulates cancer development are largely unclear. Here we show that K63-linked LKB1 polyubiquitination by Skp2-SCF ubiquitin ligase is critical for LKB1 activation by maintaining LKB1-STRAD-MO25 complex integrity. We further demonstrate that oncogenic Ras acts upstream of Skp2 to promote LKB1 polyubiquitination by activating Skp2-SCF ubiquitin ligase. Moreover, Skp2-mediated LKB1 polyubiquitination is required for energy-stress-induced cell survival. We also detected overexpression of Skp2 and LKB1 in late-stage hepatocellular carcinoma (HCC), and their overexpression predicts poor survival outcomes. Finally, we show that Skp2-mediated LKB1 polyubiquitination is important for HCC tumor growth in?vivo. Our study provides new insights into the upstream regulation of LKB1 activation and suggests a potential target, the Ras/Skp2/LKB1 axis, for cancer therapy.
    日期: 2015-03
    關聯: Molecular Cell. 2015 Mar;57(6):1022-1033.
    Link to: http://dx.doi.org/10.1016/j.molcel.2015.01.015
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1097-2765&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000351715000010
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84925272879
    显示于类别:[其他] 期刊論文

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