Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex

Qinghong Zhang, Su Yan Wang, Capucine Fleuriel, Dominique Leprince, Jonathan V. Rocheleau, David W. Piston, Richard H. Goodman

Research output: Contribution to journalArticle

144 Scopus citations

Abstract

The Sir2 histone deacetylases are important for gene regulation, metabolism, and longevity. A unique feature of these enzymes is their utilization of NAD+ as a cosubstrate, which has led to the suggestion that Sir2 activity reflects the cellular energy state. We show that SIRT1, a mammalian Sir2 homologue, is also controlled at the transcriptional level through a mechanism that is specific for this isoform. Treatment with the glycolytic blocker 2-deoxyglucose (2-DG) decreases association of the redox sensor CtBP with HIC1, an inhibitor of SIRT1 transcription. We propose that the reduction in transcriptional repression mediated by HIC1, due to the decrease of CtBP binding, increases SIKT1 expression. This mechanism allows the specific regulation of SIRT1 in response to nutrient deprivation.

Original languageEnglish (US)
Pages (from-to)829-833
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number3
DOIs
StatePublished - Jan 16 2007

Keywords

  • NAD
  • NADH
  • Redox

ASJC Scopus subject areas

  • General

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