國家衛生研究院 NHRI:Item 3990099045/5913
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/5913


    Title: Functional interaction of heat shock protein 90 and Beclin 1 modulates Toll-like receptor-mediated autophagy
    Authors: Xu, CF;Liu, J;Hsu, LC;Luo, YP;Xiang, R;Chuang, TH
    Contributors: Immunology Research Center
    Abstract: Autophagy is one of the downstream effector mechanisms for elimination of intracellular microbes following activation of the Toll-like receptors (TLRs). Although the detailed molecular mechanism for this cellular process is still unclear, Beclin 1, a key molecule for autophagy, has been suggested to play a role. Heat shock protein 90 (Hsp90) is a molecular chaperone that regulates the stability of signaling proteins. Herein, we show that Hsp90 forms a complex with Beclin 1 through an evolutionarily conserved domain to maintain the stability of Beclin 1. In monocytic cells, geldanamycin (GA), an Hsp90 inhibitor, effectively promoted proteasomal degradation of Beclin 1 in a concentration-dependent (EC(50) 100 nM) and time-dependent (t(50) 2 h) manner. In contrast, KNK437/Hsp inhibitor I had no effect. Hsp90 specifically interacted with Beclin 1 but not with other adapter proteins in the TLR signalsome. Treatment of cells with GA inhibited TLR3- and TLR4-mediated autophagy. In addition, S. typhimurium infection-induced autophagy was blocked by GA treatment. This further suggested a role of the Hsp90/Beclin 1 in controlling autophagy in response to microbial infections. Taken together, our data revealed that by maintaining the homeostasis of Beclin 1, Hsp90 plays a novel role in TLR-mediated autophagy.-Xu, C., Liu, J., Hsu, L. -C., Luo, Y., Xiang, R., Chuang, T. -H. Functional interaction of Hsp90 and Beclin 1 modulates Toll-like receptor-mediated autophagy. FASEB J. 25, 2700-2710
    Date: 2011-08
    Relation: FASEB Journal. 2011 Aug;25(8):2700-2710.
    Link to: http://dx.doi.org/10.1096/fj.10-167676
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0892-6638&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000293337800019
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=80051688648
    Appears in Collections:[Tsung-Hsien Chuang] Periodical Articles

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