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|標題:||KEAP1 E3 Ligase-Mediated Downregulation of NF-kappa B Signaling by Targeting IKK beta||作者:||Lee, D.F.
|關鍵字:||tumor angiogenesis;breast-cancer;lung-cancer;nrf2;inflammation;activation;substrate;pathway;complex;protein||Project:||Molecular Cell||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.
|Appears in Collections:||分子生物學研究所|
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