The oligomeric state of CtBP determines its role as a transcriptional co-activator and co-repressor of Wingless targets

被引:56
作者
Bhambhani, Chandan [1 ]
Chang, Jinhee L. [1 ]
Akey, David L. [2 ]
Cadigan, Ken M. [1 ]
机构
[1] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA
基金
美国国家科学基金会;
关键词
Armadillo; beta-catenin; CtBP; Wingless; Wnt; TERMINAL-BINDING-PROTEIN; NUCLEAR BETA-CATENIN; LONG-RANGE ACTION; DIRECT ASSOCIATION; SIGNALING PATHWAY; GENE-EXPRESSION; DROSOPHILA CTBP; CLEFT REGION; NAD BINDING; WNT;
D O I
10.1038/emboj.2011.100
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
C-terminal-binding protein (CtBP) is a well-characterized transcriptional co-repressor that requires homo-dimerization for its activity. CtBP can both repress and activate Wingless nuclear targets in Drosophila. Here, we examine the role of CtBP dimerization in these opposing processes. CtBP mutants that cannot dimerize are able to promote Wingless signalling, but are defective in repressing Wingless targets. To further test the role of dimerization in repression, the positions of basic and acidic residues that form inter-molecular salt bridges in the CtBP dimerization interface were swapped. These mutants cannot homo-dimerize and are compromised for repression. However, their co-expression leads to hetero-dimerization and consequent repression of Wingless targets. Our results support a model where CtBP is a gene-specific regulator of Wingless signalling, with some targets requiring CtBP dimers for inhibition while other targets utilize CtBP monomers for activation of their expression. Functional interactions between CtBP and Pygopus, a nuclear protein required for Wingless signalling, support a model where monomeric CtBP acts downstream of Pygopus in activating some Wingless targets. The EMBO Journal (2011) 30, 2031-2043. doi: 10.1038/emboj.2011.100; Published online 5 April 2011
引用
收藏
页码:2031 / 2043
页数:13
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