Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state
- PMID: 12887892
- DOI: 10.1016/s1097-2765(03)00226-0
Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state
Erratum in
- Mol Cell. 2005 Nov 11;20(3):491
Abstract
Sir2 is a NAD(+)-dependent histone deacetylase that controls gene silencing, cell cycle, DNA damage repair, and life span. Prompted by the observation that the [NAD(+)]/[NADH] ratio is subjected to dynamic fluctuations in skeletal muscle, we have tested whether Sir2 regulates muscle gene expression and differentiation. Sir2 forms a complex with the acetyltransferase PCAF and MyoD and, when overexpressed, retards muscle differentiation. Conversely, cells with decreased Sir2 differentiate prematurely. To inhibit myogenesis, Sir2 requires its NAD(+)-dependent deacetylase activity. The [NAD(+)]/[NADH] ratio decreases as muscle cells differentiate, while an increased [NAD(+)]/[NADH] ratio inhibits muscle gene expression. Cells with reduced Sir2 levels are less sensitive to the inhibition imposed by an elevated [NAD(+)]/[NADH] ratio. These results indicate that Sir2 regulates muscle gene expression and differentiation by possibly functioning as a redox sensor. In response to exercise, food intake, and starvation, Sir2 may sense modifications of the redox state and promptly modulate gene expression.
Comment in
-
Sir2 flexes its muscle.Dev Cell. 2003 Aug;5(2):188-9. doi: 10.1016/s1534-5807(03)00237-5. Dev Cell. 2003. PMID: 12919668
Similar articles
-
Sir2 flexes its muscle.Dev Cell. 2003 Aug;5(2):188-9. doi: 10.1016/s1534-5807(03)00237-5. Dev Cell. 2003. PMID: 12919668
-
Calorie restriction extends yeast life span by lowering the level of NADH.Genes Dev. 2004 Jan 1;18(1):12-6. doi: 10.1101/gad.1164804. Genes Dev. 2004. PMID: 14724176 Free PMC article.
-
Chemical activation of Sir2-dependent silencing by relief of nicotinamide inhibition.Mol Cell. 2005 Feb 18;17(4):595-601. doi: 10.1016/j.molcel.2004.12.032. Mol Cell. 2005. PMID: 15721262
-
Structure and chemistry of the Sir2 family of NAD+-dependent histone/protein deactylases.Biochem Soc Trans. 2004 Dec;32(Pt 6):904-9. doi: 10.1042/BST0320904. Biochem Soc Trans. 2004. PMID: 15506920 Review.
-
SIR2: the biochemical mechanism of NAD(+)-dependent protein deacetylation and ADP-ribosyl enzyme intermediates.Curr Med Chem. 2004 Apr;11(7):807-26. doi: 10.2174/0929867043455675. Curr Med Chem. 2004. PMID: 15078167 Review.
Cited by
-
Regulation of Muscle Stem Cell Functions: A Focus on the p38 MAPK Signaling Pathway.Front Cell Dev Biol. 2016 Aug 30;4:91. doi: 10.3389/fcell.2016.00091. eCollection 2016. Front Cell Dev Biol. 2016. PMID: 27626031 Free PMC article. Review.
-
Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration.Front Cell Dev Biol. 2022 Nov 9;10:1049653. doi: 10.3389/fcell.2022.1049653. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 36438552 Free PMC article.
-
The protein level of PGC-1α, a key metabolic regulator, is controlled by NADH-NQO1.Mol Cell Biol. 2013 Jul;33(13):2603-13. doi: 10.1128/MCB.01672-12. Epub 2013 May 6. Mol Cell Biol. 2013. PMID: 23648480 Free PMC article.
-
Divergent Transcriptional Responses to Physiological and Xenobiotic Stress in Giardia duodenalis.Antimicrob Agents Chemother. 2016 Sep 23;60(10):6034-45. doi: 10.1128/AAC.00977-16. Print 2016 Oct. Antimicrob Agents Chemother. 2016. PMID: 27458219 Free PMC article.
-
NAMPT regulates mitochondria biogenesis via NAD metabolism and calcium binding proteins during skeletal muscle contraction.J Exerc Nutrition Biochem. 2014 Sep;18(3):259-66. doi: 10.5717/jenb.2014.18.3.259. Epub 2014 Sep 11. J Exerc Nutrition Biochem. 2014. PMID: 25566462 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases