國家衛生研究院 NHRI:Item 3990099045/3930
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3930


    Title: KEAP1 E3 Ligase-Mediated Downregulation of NF-kappaB Signaling by Targeting IKKbeta
    Other Titles: KEAP1 E3 Ligase-Mediated Downregulation of NF-κB Signaling by Targeting IKKβ
    Authors: Lee, DF;Kuo, HP;Liu, M;Chou, CK;Xia, W;Du, Y;Shen, J;Chen, CT;Huo, L;Hsu, MC;Li, CW;Ding, Q;Liao, TL;Lai, CC;Lin, AC;Chang, YH;Tsai, SF;Li, LY;Hung, MC
    Contributors: Division of Molecular and Genomic Medicine
    Abstract: IκB kinase β (IKKβ) is involved in tumor development and progression through activation of the nuclear factor (NF)-κB pathway. However, the molecular mechanism that regulates IKKβ degradation remains largely unknown. Here, we show that a Cullin 3 (CUL3)-based ubiquitin ligase, Kelch-like ECH-associated protein 1 (KEAP1), is responsible for IKKβ ubiquitination. Depletion of KEAP1 led to the accumulation and stabilization of IKKβ and to upregulation of NF-κB-derived tumor angiogenic factors. A systematic analysis of the CUL3, KEAP1, and RBX1 genomic loci revealed a high percentage of genome loss and missense mutations in human cancers that failed to facilitate IKKβ degradation. Our results suggest that the dysregulation of KEAP1-mediated IKKβ ubiquitination may contribute to tumorigenesis.
    Date: 2009-10-09
    Relation: Molecular Cell. 2009 Oct 9;36(1):131-140.
    Link to: http://dx.doi.org/10.1016/j.molcel.2009.07.025
    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:000271060500013
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=70349970493
    Appears in Collections:[Shih-Feng Tsai] Periodical Articles

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