Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/60451
標題: KEAP1 E3 Ligase-Mediated Downregulation of NF-kappa B Signaling by Targeting IKK beta
作者: Lee, D.F.
賴建成
Kuo, H.P.
Liu, M.
Chou, C.K.
Xia, W.Y.
Du, Y.
Shen, J.
Chen, C.T.
Huo, L.
Hsu, M.C.
Li, C.W.
Ding, Q.Q.
Liao, T.L.
Lai, C.C.
Lin, A.C.
Chang, Y.H.
Tsai, S.F.
Li, L.Y.
Hung, M.C.
關鍵字: tumor angiogenesis
breast-cancer
lung-cancer
nrf2
inflammation
activation
substrate
pathway
complex
protein
期刊/報告no:: Molecular Cell, Volume 36, Issue 1, Page(s) 131-140.
摘要: I kappa B kinase beta (IKK beta) is involved in tumor development and progression through activation of the nuclear factor (NF)-kappa B pathway. However, the molecular mechanism that regulates IKK beta 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 IKK beta ubiquitination. Depletion of KEAP1 led to the accumulation and stabilization of IKK beta and to upregulation of NF-kappa B-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 IKK beta degradation. Our results suggest that the dysregulation of KEAP1-mediated IKK beta ubiquitination may contribute to tumorigenesis.
URI: http://hdl.handle.net/11455/60451
ISSN: 1097-2765
文章連結: http://dx.doi.org/10.1016/j.molcel.2009.07.025
Appears in Collections:分子生物學研究所

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