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Carboxyl-terminal Binding Proteins (CtBP1 and CtBP2) are transcriptional co-repressors originally identified through interactions with adenoviral E1A, implicating them in cell cycle regulation and oncogenesis. CtBPs mediate repression of genes controlling proliferation, apoptosis, adhesion, and invasiveness via PxDLS motif-dependent binding. Despite structural similarity to 2-hydroxyacid dehydrogenases, CtBPs exhibit unique nuclear and cytoplasmic roles, including Golgi fission and synaptic ribbon formation. While isoforms share overlapping expression and co-repressor complex membership, knockout studies reveal distinct developmental functions. This work explores CtBP biology, emphasizing their dual roles, protein interactions, and implications for transcriptional regulation and tumorigenesis.

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