Regulation of corepressor function by nuclear NADH

Qinghong Zhang, David W. Piston, Richard H. Goodman

Research output: Contribution to journalArticlepeer-review

456 Scopus citations

Abstract

The corepressor CtBP (carboxyl-terminal binding protein) is involved in transcriptional pathways important for development, cell cycle regulation, and transformation. We demonstrate that CtBP binding to cellular and viral transcriptional repressors is regulated by the nicotinamide adenine dinucleotides NAD+ and NADH, with NADH being two to three orders of magnitude more effective. Levels of free nuclear nicotinamide adenine dinucleotides, determined using two-photon microscopy, correspond to the levels required for half-maximal CtBP binding and are considerably lower than those previously reported. Agents capable of increasing NADH levels stimulate CtBP binding to its partners in vivo and potentiate CtBP-mediated repression. We propose that this ability to detect changes in nuclear NAD+/NADH ratio allows CtBP to serve as a redox sensor for transcription.

Original languageEnglish (US)
Pages (from-to)1895-1897
Number of pages3
JournalScience
Volume295
Issue number5561
DOIs
StatePublished - Mar 8 2002

ASJC Scopus subject areas

  • General

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