TY - JOUR
T1 - Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex
AU - Zhang, Qinghong
AU - Wang, Su Yan
AU - Fleuriel, Capucine
AU - Leprince, Dominique
AU - Rocheleau, Jonathan V.
AU - Piston, David W.
AU - Goodman, Richard H.
PY - 2007/1/16
Y1 - 2007/1/16
N2 - 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.
AB - 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.
KW - NAD
KW - NADH
KW - Redox
UR - http://www.scopus.com/inward/record.url?scp=33846505019&partnerID=8YFLogxK
U2 - 10.1073/pnas.0610590104
DO - 10.1073/pnas.0610590104
M3 - Article
C2 - 17213307
AN - SCOPUS:33846505019
SN - 0027-8424
VL - 104
SP - 829
EP - 833
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -