CIDeRGeneral Information:
| Id: | 5,241 (click here to show other Interactions for entry) |
| Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance |
| Mammalia | |
| review | |
| Reference: | Dominy JE Jr et al.(2010) Nutrient-dependent regulation of PGC-1alphas acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5 Biochim. Biophys. Acta 1804: 1676-1683 [PMID: 20005308] |
Interaction Information:
| Comment | Under high nutrient conditions and low intracellular NAD+ concentrations, PGC-1alpha is hyperacetylated by GCN5 and located within punctate nuclear bodies along with its transcription factor binding partners. In this state, the PGC-1alpha complex is effectively transcriptionally inactive. As cells are confronted with low nutrient availability, however, intracellular NAD+ levels increase and lead to an increase in the rate at which PGC-1alpha is deacetylated by Sirt1. The change in PGC-1alpha acetylation coincides with an increased occupancy of PGC-1alpha at the promoters of its target genes and an increase in transcriptional activation by remodeling of the local chromatin environment, by proteins such as p300, and greater interaction with general transcriptional machinery, facilitated by proteins such as the TRAP/Mediator complex. |
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Formal Description Interaction-ID: 51091 |
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| Comment | Sirtuin 1 (Sirt1) is a NAD+-dependent protein deacetylase that has been implicated in a panoply of physiological processes in mammals, including control of lipolytic rates in white adipose tissue, modulation of insulin secretion from pancreatic beta-cells, control of cytoplasmic and mitochondrial acetyl-CoA synthetase activity, regulation of the circadian clock, and regulation of the genetic response to various stressors such as heat shock, genotoxicity, and hypoxia. To this long list of biological functions, one can also add the regulation of PGC-1alpha acetylation state. Sirt1 has thus far been the only identified protein capable of binding to PGC-1alpha and deacetylating it both in vivo and in vitro. Sirt1 binds to a region of PGC-1alpha that is contained within amino acid residues 200–400 and deacetylates the protein in a NAD+-dependent manner. |
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Formal Description Interaction-ID: 51096 |
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| Comment | Sirtuin 1 (Sirt1) is a NAD+-dependent protein deacetylase that has been implicated in a panoply of physiological processes in mammals, including control of lipolytic rates in white adipose tissue, modulation of insulin secretion from pancreatic beta-cells, control of cytoplasmic and mitochondrial acetyl-CoA synthetase activity, regulation of the circadian clock, and regulation of the genetic response to various stressors such as heat shock, genotoxicity, and hypoxia. To this long list of biological functions, one can also add the regulation of PGC-1alpha acetylation state. Sirt1 has thus far been the only identified protein capable of binding to PGC-1alpha and deacetylating it both in vivo and in vitro. Sirt1 binds to a region of PGC-1alpha that is contained within amino acid residues 200–400 and deacetylates the protein in a NAD+-dependent manner. |
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Formal Description Interaction-ID: 51097 |
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| Comment | Sirtuin 1 (Sirt1) is a NAD+-dependent protein deacetylase that has been implicated in a panoply of physiological processes in mammals, including control of lipolytic rates in white adipose tissue, modulation of insulin secretion from pancreatic beta-cells, control of cytoplasmic and mitochondrial acetyl-CoA synthetase activity, regulation of the circadian clock, and regulation of the genetic response to various stressors such as heat shock, genotoxicity, and hypoxia. To this long list of biological functions, one can also add the regulation of PGC-1alpha acetylation state. Sirt1 has thus far been the only identified protein capable of binding to PGC-1alpha and deacetylating it both in vivo and in vitro. Sirt1 binds to a region of PGC-1alpha that is contained within amino acid residues 200–400 and deacetylates the protein in a NAD+-dependent manner. |
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Formal Description Interaction-ID: 51098 |
gene/protein affects_activity of process |
| Comment | Sirtuin 1 (Sirt1) is a NAD+-dependent protein deacetylase that has been implicated in a panoply of physiological processes in mammals, including control of lipolytic rates in white adipose tissue, modulation of insulin secretion from pancreatic beta-cells, control of cytoplasmic and mitochondrial acetyl-CoA synthetase activity, regulation of the circadian clock, and regulation of the genetic response to various stressors such as heat shock, genotoxicity, and hypoxia. To this long list of biological functions, one can also add the regulation of PGC-1alpha acetylation state. Sirt1 has thus far been the only identified protein capable of binding to PGC-1alpha and deacetylating it both in vivo and in vitro. Sirt1 binds to a region of PGC-1alpha that is contained within amino acid residues 200–400 and deacetylates the protein in a NAD+-dependent manner. |
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Formal Description Interaction-ID: 51099 |
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| Drugbank entries | Show/Hide entries for ACSS1 |
| Comment | Sirtuin 1 (Sirt1) is a NAD+-dependent protein deacetylase that has been implicated in a panoply of physiological processes in mammals, including control of lipolytic rates in white adipose tissue, modulation of insulin secretion from pancreatic beta-cells, control of cytoplasmic and mitochondrial acetyl-CoA synthetase activity, regulation of the circadian clock, and regulation of the genetic response to various stressors such as heat shock, genotoxicity, and hypoxia. To this long list of biological functions, one can also add the regulation of PGC-1alpha acetylation state. Sirt1 has thus far been the only identified protein capable of binding to PGC-1alpha and deacetylating it both in vivo and in vitro. Sirt1 binds to a region of PGC-1alpha that is contained within amino acid residues 200–400 and deacetylates the protein in a NAD+-dependent manner. |
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Formal Description Interaction-ID: 51101 |
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| Drugbank entries | Show/Hide entries for ACSS2 |
| Comment | Sirtuin 1 (Sirt1) is a NAD+-dependent protein deacetylase that has been implicated in a panoply of physiological processes in mammals, including control of lipolytic rates in white adipose tissue, modulation of insulin secretion from pancreatic beta-cells, control of cytoplasmic and mitochondrial acetyl-CoA synthetase activity, regulation of the circadian clock, and regulation of the genetic response to various stressors such as heat shock, genotoxicity, and hypoxia. To this long list of biological functions, one can also add the regulation of PGC-1alpha acetylation state. Sirt1 has thus far been the only identified protein capable of binding to PGC-1alpha and deacetylating it both in vivo and in vitro. Sirt1 binds to a region of PGC-1alpha that is contained within amino acid residues 200–400 and deacetylates the protein in a NAD+-dependent manner. |
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Formal Description Interaction-ID: 51102 |
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| Comment | Sirtuin 1 (Sirt1) is a NAD+-dependent protein deacetylase that has been implicated in a panoply of physiological processes in mammals, including control of lipolytic rates in white adipose tissue, modulation of insulin secretion from pancreatic beta-cells, control of cytoplasmic and mitochondrial acetyl-CoA synthetase activity, regulation of the circadian clock, and regulation of the genetic response to various stressors such as heat shock, genotoxicity, and hypoxia. To this long list of biological functions, one can also add the regulation of PGC-1alpha acetylation state. Sirt1 has thus far been the only identified protein capable of binding to PGC-1alpha and deacetylating it both in vivo and in vitro. Sirt1 binds to a region of PGC-1alpha that is contained within amino acid residues 200–400 and deacetylates the protein in a NAD+-dependent manner. |
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Formal Description Interaction-ID: 51104 |
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| Comment | Sirtuin 1 (Sirt1) is a NAD+-dependent protein deacetylase that has been implicated in a panoply of physiological processes in mammals, including control of lipolytic rates in white adipose tissue, modulation of insulin secretion from pancreatic beta-cells, control of cytoplasmic and mitochondrial acetyl-CoA synthetase activity, regulation of the circadian clock, and regulation of the genetic response to various stressors such as heat shock, genotoxicity, and hypoxia. To this long list of biological functions, one can also add the regulation of PGC-1alpha acetylation state. Sirt1 has thus far been the only identified protein capable of binding to PGC-1alpha and deacetylating it both in vivo and in vitro. Sirt1 binds to a region of PGC-1alpha that is contained within amino acid residues 200–400 and deacetylates the protein in a NAD+-dependent manner. |
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Formal Description Interaction-ID: 51105 |
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| Comment | Sirtuin 1 (Sirt1) is a NAD+-dependent protein deacetylase that has been implicated in a panoply of physiological processes in mammals, including control of lipolytic rates in white adipose tissue, modulation of insulin secretion from pancreatic beta-cells, control of cytoplasmic and mitochondrial acetyl-CoA synthetase activity, regulation of the circadian clock, and regulation of the genetic response to various stressors such as heat shock, genotoxicity, and hypoxia. To this long list of biological functions, one can also add the regulation of PGC-1alpha acetylation state. Sirt1 has thus far been the only identified protein capable of binding to PGC-1alpha and deacetylating it both in vivo and in vitro. Sirt1 binds to a region of PGC-1alpha that is contained within amino acid residues 200–400 and deacetylates the protein in a NAD+-dependent manner. |
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Formal Description Interaction-ID: 51107 |
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| Comment | Activation of endogenous Sirt1 activity by resveratrol in cultures of C2C12 myotubes was able to induce the deacetylation of overexpressed PGC-1alpha protein and potentiate the effects of PGC-1alpha on MCAD, ERRalpha, and cytochrome c. Resveratrol, however, was not able to enhance the activity of PGC-1alpha when all 13 of the known acetylated lysine residues were mutated to an arginine. |
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Formal Description Interaction-ID: 51108 |
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| Drugbank entries | Show/Hide entries for Resveratrol |
| Comment | Overexpression of Sirt1 in the liver significantly increased the expression of PEPCK and glucose-6-phosphatase in a PGC-1alpha-dependent manner. |
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Formal Description Interaction-ID: 51115 |
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| Drugbank entries | Show/Hide entries for PCK1 |
| Comment | Overexpression of Sirt1 in the liver significantly increased the expression of PEPCK and glucose-6-phosphatase in a PGC-1alpha-dependent manner. |
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Formal Description Interaction-ID: 51118 |
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| Comment | Levels of Sirt1 have been reported to change in response to nutrients. Some investigators have found that Sirt1 transcription is inversely responsive to changes in nutrient load by a mechanism that is dependent upon either the transcription factor Foxo3a or the transcriptional co-repressor CtBp and its binding partner Hypermethylated In Cancer. Others, however, report that there are increases in Sirt1 protein caused by nutrient deprivation in both cultured cells and mice, but are not accompanied by changes in the rates of transcription or in steady-state mRNA levels. Among these reports there is disagreement as to whether Sirt1 actually increases in the liver. From this body of work, it is clear that additional studies need to be done to establish the exact mechanism by which Sirt1 protein is controlled by nutriture and if this control is cell autonomous or tissue specific. |
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Formal Description Interaction-ID: 51121 |
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