Nicotinamide adenine dinucleotide stimulates oligomerization, interaction with adenovirus E1A and an intrinsic dehydrogenase activity of CtBP

The C-terminal region of adenovirus E1A interacts with the transcriptional corepressor, CtBP. The mechanism of transcriptional regulation by CtBP is not known. CtBP shares a significant homology with NAD(+)-dependent D2-hydroxy acid dehydrogenases. CtBP binds to NAD(+) and NADH. Both forms of the dinucleotide stimulate oligomerization of native CtBP and enhance complex formation with E1A. CtBP also has a slow dehydrogenase activity. Interaction of CtBP with E1A reduces the dehydrogenase activity. Our results raise the possibility that the oxidation/reduction reactions of CtBP may regulate transcription. Thus, CtBP is a unique transcriptional regulator with an enzymatic activity similar to metabolic dehydrogenases. The levels of intracellular nicotinamide adenine dinucleotide may modulate transcriptional activity of CtBP. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.