title: The oligomeric state of CtBP determines its role as a transcriptional co-activator and co-repressor of Wingless targets.
abstract: 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.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Chandan
authors.initials: C
authors.lastname: Bhambhani
authors.forename: Jinhee L
authors.initials: JL
authors.lastname: Chang
authors.forename: David L
authors.initials: DL
authors.lastname: Akey
authors.forename: Ken M
authors.initials: KM
authors.lastname: Cadigan
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D056970:Co-Repressor Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D008954:Models, Biological; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D014157:Transcription Factors / Q000378:metabolism; D051155:Wnt1 Protein / Q000096:biosynthesis*
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050505:Mutant Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C074622:wg protein, Drosophila; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein