Role of NAD binding and catalytic residues in the C-terminal binding protein corepressor

Mani-Telang, Priya; Sutrias-Grau, Montserrat; Williams, Geoffrey; Arnosti, David N.

doi:10.1016/j.febslet.2007.10.011

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Volume 581, Issue 27 , Pages 5241-5246, 13 November 2007

Role of NAD binding and catalytic residues in the C-terminal binding protein corepressor

Edited by Francesc Posas

Priya Mani-Telang
- Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA
- Oregon Health and Science University, 3181 SW Sam Jackson Park Road, L606 Portland, OR 97239, USA
Montserrat Sutrias-Grau
- Floridablanca 26, 08191 Rubi, Barcelona, Spain
Geoffrey Williams
- Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Box G-B187, Providence, RI 02912, USA
David N. Arnosti
- Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA
- Department of Biochemistry and Molecular Biology, 413 Biochemistry, Michigan State University, East Lansing, MI 48824, USA
- Corresponding author. Address: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. Fax: +1 517 353 9334.

Received 27 April 2007; received in revised form 20 August 2007; accepted 5 October 2007. published online 12 October 2007.

Abstract

CtBP corepressor proteins potentiate the activity of many metazoan transcriptional repressors. These proteins are homologous to prokaryotic D-2-hydroxyacid dehydrogenases, possessing an NAD/NADH binding fold and conserved active site residues. When expressed in Drosophila, a catalytic site mutant retains biological activity, however, we find that an NAD binding mutant lacks biological activity. The NAD mutant, similar to a dimerization mutant, is expressed at low levels, indicating that binding of NAD/NADH may affect CtBP stability. These data support the idea that the ancestral dehydrogenase activity is not required for CtBP function, and NAD binding may play a regulatory, rather than catalytic, role.

Keywords: Corepressor, C-terminal binding protein, CtBP, Transcriptional repression