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CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability
Author(s) -
Noriega Lilia G,
Feige Jérôme N,
Canto Carles,
Yamamoto Hiroyasu,
Yu Jiujiu,
Herman Mark A,
Mataki Chikage,
Kahn Barbara B,
Auwerx Johan
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.151
Subject(s) - nad+ kinase , sirtuin 1 , calorie restriction , creb , carbohydrate responsive element binding protein , downregulation and upregulation , cyclic amp response element binding protein , nicotinamide phosphoribosyltransferase , nicotinamide adenine dinucleotide , regulator , microbiology and biotechnology , biochemistry , chemistry , biology , transcription factor , endocrinology , enzyme , gene
The nicotinamide adenine dinucleotide (NAD + )‐dependent deacetylase SIRT1 is a major metabolic regulator activated by energy stresses such as fasting or calorie restriction. SIRT1 activation during fasting not only relies on the increase in the NAD + /NADH ratio caused by energy deprivation but also involves an upregulation of SIRT1 mRNA and protein levels in various metabolic tissues. We demonstrate that SIRT1 expression is controlled systemically by the activation of the cyclic AMP response‐element‐binding protein upon low nutrient availability. Conversely, in the absence of energetic stress, the carbohydrate response‐element‐binding protein represses the expression of SIRT1 . Altogether, these results demonstrate that SIRT1 expression is tightly controlled at the transcriptional level by nutrient availability and further underscore that SIRT1 is a crucial metabolic checkpoint connecting the energetic status with transcriptional programmes.