The CtBP family: enigmatic and enzymatic transcriptional co-repressors

Transcription factors that associate with DNA sequences in promoters and en hancers often recruit co-regulators that modulate their activity. Many of t hese co-regulators have intrinsic enzymatic activity and influence gene exp ression by modifying chromatin and altering its structure. Recently, a new family of co-repressors, the C-terminal binding proteins, has been describe d. These proteins recognize Pro-X-Asp-Leu-Ser (PXDLS) motifs in DNA-binding proteins and function as transcriptional corepressors in Drosophila, Xenop us and mammals. The precise mechanisms by which they influence transcriptio n are still under investigation. CtBP proteins dimerize and can contact his tone deacetylases; hence they may operate by linking deacetylases to DNA-bo und factors. But it appears that CtBP proteins also have intrinsic enzymati c activity. They have significant homology to D-isomer-specific 2-hydroxy a cid dehydrogenases, and remarkably one family member, rat CtBP, has been sh own to have a second role, functioning as an acyl transferase in Golgi main tenance. These observations raise the possibility that CtBP proteins might regulate gene expression directly by means of their enzymatic activities, i n addition to serving as simple bridging proteins. Supplementary material f or this article can be found on the BioEssays homepage at http://www.inters cience. wiley.com/jpages/0265-9247/suppmattv23_8.684. (C) 2001 John Wiley & Sons, Inc.