國家衛生研究院 NHRI:Item 3990099045/10231
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    题名: K48-linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression
    作者: Hao, Z;Sheng, Y;Duncan, GS;Li, WY;Dominguez, C;Sylvester, J;Su, YW;Lin, GH;Snow, BE;Brenner, D;You-Ten, A;Haight, J;Inoue, S;Wakeham, A;Elford, A;Hamilton, S;Liang, Y;Zuniga-Pflucker, JC;He, HH;Ohashi, PS;Mak, TW
    贡献者: Immunology Research Center
    摘要: T-cell proliferation is regulated by ubiquitination but the underlying molecular mechanism remains obscure. Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase. Mule is elevated in T cells upon TCR engagement, and Mule deficiency in T cells blocks proliferation because KLF4 accumulates and drives upregulation of its transcriptional targets E2F2 and the cyclin-dependent kinase inhibitors p21 and p27. T-cell-specific Mule knockout (TMKO) mice develop exacerbated experimental autoimmune encephalomyelitis (EAE), show impaired generation of antigen-specific CD8+ T cells with reduced cytokine production, and fail to clear LCMV infections. Thus, Mule-mediated ubiquitination of the novel substrate KLF4 regulates T-cell proliferation, autoimmunity and antiviral immune responses in vivo.
    日期: 2017-01-13
    關聯: Nature Communications. 2017 Jan 13;8:Article number 14003.
    Link to: http://dx.doi.org/10.1038/ncomms14003
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-1723&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000391936100001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85009436144
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