國家衛生研究院 NHRI:Item 3990099045/5429
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    題名: 14-3-3 sigma regulates B-cell homeostasis through stabilization of FOXO1
    其他題名: 14-3-3σ regulates B-cell homeostasis through stabilization of FOXO1
    作者: Su, YW;Hao, ZY;Hirao, A;Yamamoto, K;Lin, WJ;Young, A;Duncan, GS;Yoshida, H;Wakeham, A;Lang, PA;Murakami, K;Ohashi, P;Mak, TW
    貢獻者: Immunology Research Center
    摘要: 14-3-3 sigma regulates cytokinesis and cell cycle arrest induced by DNA damage but its role in the immune system is unknown. Using gene-targeted 14-3-3 sigma-deficient (i.e., KO) mice, we studied the role of 14-3-3 sigma in B-cell functions. Total numbers of B cells were reduced by spontaneous apoptosis of peripheral B cells. Upon B-cell antigen receptor engagement in vitro, KO B cells did not proliferate properly or up-regulate CD86. In response to T cell-independent antigens, KO B cells showed poor secretion of antigen-specific IgM. This deficit led to increased lethality of KO mice after vesicular stomatitis virus infection. KO B cells showed elevated total FOXO transcriptional activity but also increased FOXO1 degradation. Coimmunoprecipitation revealed that endogenous 14-3-3 sigma protein formed a complex with FOXO1 protein. Our results suggest that 14-3-3 sigma maintains FOXO1 at a consistent level critical for normal B-cell antigen receptor signaling and B-cell survival.
    日期: 2011-01
    關聯: Proceedings of the National Academy of Sciences of the United States of America. 2011 Jan;108(4):1555-1560.
    Link to: http://dx.doi.org/10.1073/pnas.1017729108
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8424&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000286594800065
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79952119593
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