國家衛生研究院 NHRI:Item 3990099045/10103
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10103


    Title: TRAF6 restricts p53 mitochondrial translocation, apoptosis, and tumor suppression
    Authors: Zhang, X;Li, CF;Zhang, L;Wu, CY;Han, L;Jin, G;Rezaeian, AH;Han, F;Liu, C;Xu, C;Xu, X;Huang, CY;Tsai, FJ;Tsai, CH;Watabe, K;Lin, HK
    Contributors: National Institute of Cancer Research
    Abstract: Mitochondrial p53 is involved in apoptosis and tumor suppression. However, its regulation is not well studied. Here, we show that TRAF6 E3 ligase is a crucial factor to restrict mitochondrial translocation of p53 and spontaneous apoptosis by promoting K63-linked ubiquitination of p53 at K24 in cytosol, and such ubiquitination limits the interaction between p53 and MCL-1/BAK. Genotoxic stress reduces this ubiquitination in cytosol by S13/T330 phosphorylation-dependent translocation of TRAF6 from cytosol to nucleus, where TRAF6 also facilitates the K63-linked ubiquitination of nuclear p53 and its transactivation by recruiting p300 for p53 acetylation. Functionally, K63-linked ubiquitination of p53 compromised p53-mediated apoptosis and tumor suppression. Colorectal cancer samples with WT p53 reveal that TRAF6 overexpression negatively correlates with apoptosis and predicts poor response to chemotherapy and radiotherapy. Together, our study identifies TRAF6 as a critical gatekeeper to restrict p53 mitochondrial translocation, and such mechanism may contribute to tumor development and drug resistance.
    Date: 2016-11-17
    Relation: Molecular Cell. 2016 Nov 17;64(4):803-814.
    Link to: http://dx.doi.org/10.1016/j.molcel.2016.10.002
    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:000389515400016
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84995560687
    Appears in Collections:[Others] Periodical Articles

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