KEAP1 E3 ligase-mediated down regulation of NF-B signaling by targeting IKK.

ASIA unversity > 醫學暨健康學院 > 生物科技學系 > 期刊論文 > Item 310904400/16123

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題名:	KEAP1 E3 ligase-mediated down regulation of NF-B signaling by targeting IKK.
作者:	Lee, D-F;Kuo, H-P;Liu, M;Chou, C-K;Xia, W;Du, Y.;Shen, J;Chen, C-T;Huo, L;Hsu, M-C;Li, C-W;Ding, Q;Liao, T-L;Lai, C-C;Lin, A-C;Chang, Y-H;Tsai, S-F;李龍緣;Li, Long-Yuan;洪明奇;Hung, Mien-Chie
貢獻者:	生物科技學系
日期:	2009
上傳時間:	2012-11-23 09:08:50 (UTC+0)
摘要:	IkappaB kinase beta (IKKbeta) is involved in tumor development and progression through activation of the nuclear factor (NF)-kappaB pathway. However, the molecular mechanism that regulates IKKbeta 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 IKKbeta ubiquitination. Depletion of KEAP1 led to the accumulation and stabilization of IKKbeta and to upregulation of NF-kappaB-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 IKKbeta degradation. Our results suggest that the dysregulation of KEAP1-mediated IKKbeta ubiquitination may contribute to tumorigenesis.
關聯:	MOLECULAR CELL, V036 N.1:131–140.
顯示於類別:	[生物科技學系] 期刊論文

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