KEAP1 E3 Ligase-Mediated Downregulation of NF-kappa B Signaling by Targeting IKK beta

ASIAIR > College of Medical and Health Science > Department of Biotechnology > Journal Article > Item 310904400/8205

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Title:	KEAP1 E3 Ligase-Mediated Downregulation of NF-kappa B Signaling by Targeting IKK beta
Authors:	Lee, DF (Lee, Dung-Fang);Kuo, HP (Kuo, Hsu-Ping);Liu, M (Liu, Mo);Chou, CK (Chou, Chao-Kai);Xia, WY (Xia, Weiya);Du, Y (Du, Yi);Shen, J (Shen, Jia);Chen, CT (Chen, Chun-Te);Huo, L (Huo, Longfei);Hsu, MC (Hsu, Ming-Chuan);Li, CW (Li, Chia-Wei);Ding, QQ (Ding, Qingqing);Liao, TL (Liao, Tsai-Lien);Lai, CC (Lai, Chien-Chen);Lin, AC (Lin, Ann-Chi);Chang, YH (Chang, Ya-Hui);Tsai, SF (Tsai, Shih-Feng);Li, LY (Li, Long-Yuan);Hung, MC (Hung, Mien-Chie)
Contributors:	Department of Biotechnology
Keywords:	TUMOR ANGIOGENESIS;BREAST-CANCER;LUNG-CANCER;NRF2;INFLAMMATION;ACTIVATION;SUBSTRATE;PATHWAY;COMPLEX;PROTEIN
Date:	2009-10
Issue Date:	2010-03-26 02:29:01 (UTC+0)
Publisher:	Asia University
Abstract:	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.
Relation:	MOLECULAR CELL 36 (1): 131-140
Appears in Collections:	[Department of Biotechnology] Journal Article

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