期刊
MOLECULAR CELL
卷 16, 期 2, 页码 245-255出版社
CELL PRESS
DOI: 10.1016/j.molcel.2004.10.010
关键词
-
资金
- NCI NIH HHS [CA78595, CA110552, CA104397, CA095644] Funding Source: Medline
Understanding how signaling cascades stimulate chromatin-remodeling events through derepression is one of the foremost questions in the transcription field. Here, we demonstrate that NF-kappaB transcription requires IKKalpha to phosphorylate SMRT on chromatin, stimulating the exchange of corepressor for coactivator complexes. IKKalpha-induced phosphorylation coincides with a loss of chromatin-associated SMRT and HDAC3 and with nuclear export of the SMRT corepressor, events required for expression of the NF-kappaB-regulated clAP-2 and IL-8 genes. Although SMRT derepression corresponds with the recruitment of TBL1 /TBLR1, this complex alone is insufficient to relieve repression. Using a nonphosphorylatable SMRT protein, we demonstrate that IKKa-induced phosphorylation is required to recruit 14-3-3epsilon and Ubc5 for SMRT derepression. Failure of IKKalpha to stimulate the removal of SMRT from chromatin inhibits the recruitment of NF-kappaB to promoters, blocking transcription and sensitizing cells to apoptosis. Our work provides evidence that IKKalpha orchestrates SMRT derepression, a prerequisite for NF-kappaB transcription and survival.
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