Phosphorylation of CBP by IKKα Promotes Cell Growth by Switching the Binding Preference of CBP from p53 to NF-κB

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 台中附設醫院 > 期刊論文 > Item 310903500/2458

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题名:	Phosphorylation of CBP by IKKα Promotes Cell Growth by Switching the Binding Preference of CBP from p53 to NF-κB
作者:	黃偉謙(Wei-Chien Huang);(Tsai-Kai Ju);洪明奇;(Ching-Chow Chen)
贡献者:	中國附醫分子醫學中心
关键词:	DNA;SIGNALING;CELLCYCLE
日期:	2007-04
上传时间:	2009-08-20 17:30:58 (UTC+8)
摘要:	CBP plays a central role in coordinating and integrating multiple signaling pathways. Competition between NF-κB and p53 for CBP is a crucial determinant of whether a cell proliferates or undergoes apoptosis. However, how the CBP-dependent crosstalk between these two transcription factors is regulated remains unclear. Here, we show that IKKα phosphorylates CBP at serine 1382 and serine 1386 and consequently increases CBP's HAT and transcriptional activities. Importantly, such phosphorylation enhances NF-κB-mediated gene expression and suppresses p53-mediated gene expression by switching the binding preference of CBP from p53 to NF-κB, thus promoting cell growth. The CBP phosphorylation also correlates with constitutive IKKα activation in human lung tumor tissue compared with matched nontumor lung tissue. Our results suggest that phosphorylation of CBP by IKKα regulates the CBP-mediated crosstalk between NF-κB and p53 and thus may be a critical factor in the promotion of cell proliferation and tumor growth.
關聯:	MOLECULAR CELL 26(1):75~87
显示于类别:	[台中附設醫院] 期刊論文

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