CtBP2 and its homolog CtBP1 are transcriptional co-repressors originally identified as proteins that bind the carboxy-terminus of the human adenovirus E1A protein. CtBP proteins are thought to play important roles in regulating various developmental pathways because deletion of CtBP2 leads to embryonic lethality at E10.5 and is correlated with axial patterning defects. CtBP proteins regulate various oncogenic signaling pathways as promoters of epithelial-mesenchymal transition, apoptosis antagonists, and tumor suppressor genes repressors. The CtBP protein transcription co-repression activity results from interactions with numerous transcription factors and chromatin modulators, including the polycomb group proteins. Depending on the context, CtBP proteins interact with a short amino acid sequence motif to mediate repression of target genes through both histone deacetylase-dependent and independent mechanisms. CtBP proteins display a high sequence homology to the bacterial D-isomer-specific 2-hydroxyacid dehydrogenase enzymes. Research studies indicate that nuclear NADH levels regulate CtBP transcription repression activities, as NADH binding is required for CtBP2 homodimerization and transcription co-repressor activity.
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