title: C-terminal binding proteins: central players in development and disease.
abstract: C-terminal binding proteins (CtBPs) were initially identified as binding partners for the E1A-transforming proteins. Although the invertebrate genome encodes one CtBP protein, two CtBPs (CtBP1 and CtBP2) are encoded by the vertebrate genome and perform both unique and duplicative functions. CtBP1 and CtBP2 are closely related and act as transcriptional corepressors when activated by nicotinamide adenine dinucleotide binding to their dehydrogenase domains. CtBPs exert transcriptional repression primarily via recruitment of a corepressor complex to DNA that consists of histone deacetylases (HDACs) and histone methyltransferases, although CtBPs can also repress transcription through HDAC-independent mechanisms. More recent studies have demonstrated a critical function for CtBPs in the transcriptional repression of pro-apoptotic genes such as Bax, Puma, Bik, and Noxa. Nonetheless, although recent efforts have characterized the essential involvement of CtBPs in promoting cellular survival, the dysregulation of CtBPs in both neurodegenerative disease and cancers remains to be fully elucidated.
authors.forename: Trisha R
authors.initials: TR
authors.lastname: Stankiewicz
authors.forename: Josie J
authors.initials: JJ
authors.lastname: Gray
authors.forename: Aimee N
authors.initials: AN
authors.lastname: Winter
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Linseman
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048788:Growth and Development; D006801:Humans; D009243:NAD / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D015533:Transcriptional Activation
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009243:NAD; D000429:Alcohol Oxidoreductases; C421248:CTBP2 protein, human; C096794:C-terminal binding protein