The CtBP Family: Enigmatic and Enzymatic Transcriptional Co-repressors

Transcription factors that associate with DNA sequences in promoters and enhancers often recruit co-regulators that modulate their activity. Many of these co-regulators have intrinsic enzymatic activity and influence gene expression by modifying chromatin and altering its structure. Recently, a new family of co-repressors, the C-terminal binding proteins, has been described. These proteins recognize Pro-X-Asp-Leu-Ser (PXDLS) motifs in DNA-binding proteins and function as transcriptional co-repressors in Drosophila, Xenopus and mammals. The precise mechanisms by which they influence transcription are still under investigation. CtBP proteins dimerize and can contact histone deacetylases; hence they may operate by linking deacetylases to DNA-bound factors. But it appears that CtBP proteins also have intrinsic enzymatic activity. They have significant homology to D-isomer-specific 2-hydroxy acid dehydrogenases, and remarkably one family member, rat CtBP, has been shown to have a second role, functioning as an acyl transferase in Golgi maintenance. These observations raise the possibility that CtBP proteins might regulate gene expression directly by means of their enzymatic activities, in addition to serving as simple bridging proteins. Supplementary material for this article can be found on the BioEssays homepage at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/v23_8.684.