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'''Peroxisome proliferator-activated receptor gamma coactivator 1-alpha''' (PGC-1alpha) is a [[protein]] that in humans is encoded by the ''PPARGC1A'' [[gene]].<ref name="pmid10585775">{{cite journal | author = Esterbauer H, Oberkofler H, Krempler F, Patsch W | title = Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression | journal = Genomics | volume = 62 | issue = 1 | pages = 98–102 | year = 2000 | month = Feb | pmid = 10585775 | pmc = | doi = 10.1006/geno.1999.5977 }}</ref>
'''Peroxisome proliferator-activated receptor gamma coactivator 1-alpha''' (PGC-1alpha) is a [[protein]] that in humans is encoded by the ''PPARGC1A'' [[gene]].<ref name="pmid10585775">{{cite journal | author = Esterbauer H, Oberkofler H, Krempler F, Patsch W | title = Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression | journal = Genomics | volume = 62 | issue = 1 | pages = 98–102 | year = 2000 | month = Feb | pmid = 10585775 | pmc = | doi = 10.1006/geno.1999.5977 }}</ref>


PPARGC1A is also known as [[human accelerated regions|human accelerated region]] 20. It may, therefore, have played a key role in differentiating humans from apes.<ref name="Pollard2006">{{cite journal |author=Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M Jr, Vanderhaeghen P, Haussler D |title=An RNA gene expressed during cortical development evolved rapidly in humans |journal=Nature |volume=443 |issue=7108 |page=167–172 |date=2006-08-16 |pmid=16915236 |doi=10.1038/nature05113 |pages=167–72}} [http://www.nature.com/nature/journal/v443/n7108/extref/nature05113-s1.doc supplement]</ref>
PPARGC1A is also known as [[human accelerated regions|human accelerated region]] 20. It may, therefore, have played a key role in differentiating humans from apes.<ref name="Pollard2006">{{cite journal |author=Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M Jr, Vanderhaeghen P, Haussler D |title=An RNA gene expressed during cortical development evolved rapidly in humans |journal=Nature |volume=443 |issue=7108 |pages=167–172 |date=2006-08-16 |pmid=16915236 |doi=10.1038/nature05113 |pages=167–72}} [http://www.nature.com/nature/journal/v443/n7108/extref/nature05113-s1.doc supplement]</ref>


PGC-1alpha is a transcriptional [[Coactivator (genetics)|coactivator]] that regulates the genes involved in [[energy metabolism]]. This protein interacts with the [[nuclear receptor]] [[PPARG|PPAR-γ]], which permits the interaction of this protein with multiple [[transcription factor]]s. This protein can interact with, and regulate the activities of, cAMP response element-binding protein ([[CREB]]) and nuclear respiratory factors [[NRF1|(NRFs)]]. It provides a direct link between external physiological stimuli and the regulation of [[mitochondrion|mitochondrial]] biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity.<ref>{{cite web | title = Entrez Gene: PPARGC1A peroxisome proliferator-activated receptor gamma, coactivator 1 alpha| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10891| accessdate = }}</ref>
PGC-1alpha is a transcriptional [[Coactivator (genetics)|coactivator]] that regulates the genes involved in [[energy metabolism]]. This protein interacts with the [[nuclear receptor]] [[PPARG|PPAR-γ]], which permits the interaction of this protein with multiple [[transcription factor]]s. This protein can interact with, and regulate the activities of, cAMP response element-binding protein ([[CREB]]) and nuclear respiratory factors [[NRF1|(NRFs)]]. It provides a direct link between external physiological stimuli and the regulation of [[mitochondrion|mitochondrial]] biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity.<ref>{{cite web | title = Entrez Gene: PPARGC1A peroxisome proliferator-activated receptor gamma, coactivator 1 alpha| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10891| accessdate = }}</ref>


== Regulation ==
== Regulation ==
PGC-1α is thought to be a master integrator of external signals.
PGC-1α is thought to be a master integrator of external signals.
It is known to be activated by a host of factors, including:
It is known to be activated by a host of factors, including:


# Reactive oxygen species [[reactive oxygen species|(ROS)]] and reactive nitrogen species [[reactive nitrogen species|(RNS)]], both formed endogenously in the cell as by-products of metabolism but upregulated during times of cellular stress.
# Reactive oxygen species [[reactive oxygen species|(ROS)]] and reactive nitrogen species [[reactive nitrogen species|(RNS)]], both formed endogenously in the cell as by-products of metabolism but upregulated during times of cellular stress.
# cAMP response element-binding ([[CREB]]) proteins, activated by an increase in cAMP following external cellular signals.
# cAMP response element-binding ([[CREB]]) proteins, activated by an increase in cAMP following external cellular signals.
# Protein kinase B / [[Akt]] is thought to downregulate PGC-1α, but upregulate its downstream effectors, NRF1 and NRF2. Akt itself is activated by PIP3, often upregulated by IP3K after G-protein signals. The Akt family is also known to activate pro-survival signals as well as metabolic activation.
# Protein kinase B / [[Akt]] is thought to downregulate PGC-1α, but upregulate its downstream effectors, NRF1 and NRF2. Akt itself is activated by PIP3, often upregulated by IP3K after G-protein signals. The Akt family is also known to activate pro-survival signals as well as metabolic activation.
# [[SIRT1]] binds and activates PGC-1α through deacetylation.
# [[SIRT1]] binds and activates PGC-1α through deacetylation.


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== Interactions ==
== Interactions ==


PPARGC1A has been shown to [[Protein-protein_interaction|interact]] with:
PPARGC1A has been shown to [[Protein-protein interaction|interact]] with:
* [[CREB-binding protein]]<ref name="pmid10558993">{{cite journal | author = Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM | title = Activation of PPARgamma coactivator-1 through transcription factor docking | journal = Science | volume = 286 | issue = 5443 | pages = 1368–71 | year = 1999 | month = November | pmid = 10558993 | doi = 10.1126/science.286.5443.1368| url = }}</ref>
* [[CREB-binding protein]]<ref name="pmid10558993">{{cite journal | author = Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM | title = Activation of PPARgamma coactivator-1 through transcription factor docking | journal = Science | volume = 286 | issue = 5443 | pages = 1368–71 | year = 1999 | month = November | pmid = 10558993 | doi = 10.1126/science.286.5443.1368| url = }}</ref>
* [[Farnesoid X receptor]]<ref name="pmid14729567">{{cite journal | author = Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ, Edwards PA | title = Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) regulates triglyceride metabolism by activation of the nuclear receptor FXR | journal = Genes Dev. | volume = 18 | issue = 2 | pages = 157–69 | year = 2004 | month = January | pmid = 14729567 | pmc = 324422 | doi = 10.1101/gad.1138104 | url = }}</ref>
* [[Farnesoid X receptor]]<ref name="pmid14729567">{{cite journal | author = Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ, Edwards PA | title = Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) regulates triglyceride metabolism by activation of the nuclear receptor FXR | journal = Genes Dev. | volume = 18 | issue = 2 | pages = 157–69 | year = 2004 | month = January | pmid = 14729567 | pmc = 324422 | doi = 10.1101/gad.1138104 | url = }}</ref>
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* [[MED1]]<ref name=pmid14636573/> [[MED12]]<ref name=pmid14636573/> [[MED14]]<ref name=pmid14636573/> [[MED17]]<ref name="pmid14636573">{{cite journal | author = Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG | title = Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha | journal = Mol. Cell | volume = 12 | issue = 5 | pages = 1137–49 | year = 2003 | month = November | pmid = 14636573 | doi = 10.1016/S1097-2765(03)00391-5| url = }}</ref>
* [[MED1]]<ref name=pmid14636573/> [[MED12]]<ref name=pmid14636573/> [[MED14]]<ref name=pmid14636573/> [[MED17]]<ref name="pmid14636573">{{cite journal | author = Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG | title = Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha | journal = Mol. Cell | volume = 12 | issue = 5 | pages = 1137–49 | year = 2003 | month = November | pmid = 14636573 | doi = 10.1016/S1097-2765(03)00391-5| url = }}</ref>
* [[NRF1]]<ref name="pmid10412986">{{cite journal | author = Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM | title = Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1 | journal = Cell | volume = 98 | issue = 1 | pages = 115–24 | year = 1999 | month = July | pmid = 10412986 | doi = 10.1016/S0092-8674(00)80611-X | url = }}</ref>
* [[NRF1]]<ref name="pmid10412986">{{cite journal | author = Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM | title = Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1 | journal = Cell | volume = 98 | issue = 1 | pages = 115–24 | year = 1999 | month = July | pmid = 10412986 | doi = 10.1016/S0092-8674(00)80611-X | url = }}</ref>
* [[Peroxisome proliferator-activated receptor gamma]]<ref name=pmid14636573/><ref name=pmid10558993/>
* [[Peroxisome proliferator-activated receptor gamma]]<ref name=pmid10558993/><ref name=pmid14636573/>
* [[Retinoid X receptor alpha]].<ref name="pmid11714715">{{cite journal | author = Delerive P, Wu Y, Burris TP, Chin WW, Suen CS | title = PGC-1 functions as a transcriptional coactivator for the retinoid X receptors | journal = J. Biol. Chem. | volume = 277 | issue = 6 | pages = 3913–7 | year = 2002 | month = February | pmid = 11714715 | doi = 10.1074/jbc.M109409200 | url = }}</ref>
* [[Retinoid X receptor alpha]].<ref name="pmid11714715">{{cite journal | author = Delerive P, Wu Y, Burris TP, Chin WW, Suen CS | title = PGC-1 functions as a transcriptional coactivator for the retinoid X receptors | journal = J. Biol. Chem. | volume = 277 | issue = 6 | pages = 3913–7 | year = 2002 | month = February | pmid = 11714715 | doi = 10.1074/jbc.M109409200 | url = }}</ref>
* [[Thyroid hormone receptor beta]]<ref name=pmid11751919>{{cite journal |last=Wu |first=Yifei |authorlink= |coauthors=Delerive Philippe, Chin William W, Burris Thomas P |year=[[2002]]|month=Mar. |title=Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1 |journal=J. Biol. Chem. |volume=277 |issue=11 |pages=8898–905 |publisher= |location = United States| issn = 0021-9258| pmid = 11751919 |doi = 10.1074/jbc.M110761200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>
* [[Thyroid hormone receptor beta]]<ref name=pmid11751919>{{cite journal |last=Wu |first=Yifei |authorlink= |coauthors=Delerive Philippe, Chin William W, Burris Thomas P |year=[[2002]]|month=Mar. |title=Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1 |journal=J. Biol. Chem. |volume=277 |issue=11 |pages=8898–905 |publisher= |location = United States| issn = 0021-9258| pmid = 11751919 |doi = 10.1074/jbc.M110761200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>
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==References==
==References==
{{reflist|2}}
{{Reflist|2}}


==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
{{PBB_Further_reading
| citations =
| citations =
*{{cite journal | author=Knutti D, Kralli A |title=PGC-1, a versatile coactivator |journal=Trends Endocrinol. Metab. |volume=12 |issue= 8 |pages= 360–5 |year= 2001 |pmid= 11551810 |doi=10.1016/S1043-2760(01)00457-X }}
*{{cite journal | author=Knutti D, Kralli A |title=PGC-1, a versatile coactivator |journal=Trends Endocrinol. Metab. |volume=12 |issue= 8 |pages= 360–5 |year= 2001 |pmid= 11551810 |doi=10.1016/S1043-2760(01)00457-X }}
*{{cite journal | author=Puigserver P, Spiegelman BM |title=Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator |journal=Endocr. Rev. |volume=24 |issue= 1 |pages= 78–90 |year= 2003 |pmid= 12588810 |doi=10.1210/er.2002-0012 }}
*{{cite journal | author=Puigserver P, Spiegelman BM |title=Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator |journal=Endocr. Rev. |volume=24 |issue= 1 |pages= 78–90 |year= 2003 |pmid= 12588810 |doi=10.1210/er.2002-0012 }}
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* {{FactorBook|PGC1A}}
* {{FactorBook|PGC1A}}


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{{Transcription coregulators}}
{{Transcription coregulators}}
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[[Category:Gene expression]]
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[[Category:Transcription coregulators]]


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Revision as of 14:37, 14 November 2011

Template:PBB Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) is a protein that in humans is encoded by the PPARGC1A gene.[1]

PPARGC1A is also known as human accelerated region 20. It may, therefore, have played a key role in differentiating humans from apes.[2]

PGC-1alpha is a transcriptional coactivator that regulates the genes involved in energy metabolism. This protein interacts with the nuclear receptor PPAR-γ, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element-binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity.[3]

Regulation

PGC-1α is thought to be a master integrator of external signals. It is known to be activated by a host of factors, including:

  1. Reactive oxygen species (ROS) and reactive nitrogen species (RNS), both formed endogenously in the cell as by-products of metabolism but upregulated during times of cellular stress.
  2. cAMP response element-binding (CREB) proteins, activated by an increase in cAMP following external cellular signals.
  3. Protein kinase B / Akt is thought to downregulate PGC-1α, but upregulate its downstream effectors, NRF1 and NRF2. Akt itself is activated by PIP3, often upregulated by IP3K after G-protein signals. The Akt family is also known to activate pro-survival signals as well as metabolic activation.
  4. SIRT1 binds and activates PGC-1α through deacetylation.

Clinical significance

Recently PPARGC1A has been implicated as a potential therapy for Parkinson's Disease conferring protective effects on mitochondrial metabolism.[4]

Interactions

PPARGC1A has been shown to interact with:

ERRalpha and PGC-1alpha are coactivators of both Glucokinase (GK) and SIRT3, binding to an ERRE elements in the GK and SIRT3 promoters.

See also

References

  1. ^ Esterbauer H, Oberkofler H, Krempler F, Patsch W (2000). "Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression". Genomics. 62 (1): 98–102. doi:10.1006/geno.1999.5977. PMID 10585775. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M Jr, Vanderhaeghen P, Haussler D (2006-08-16). "An RNA gene expressed during cortical development evolved rapidly in humans". Nature. 443 (7108): 167–72. doi:10.1038/nature05113. PMID 16915236.{{cite journal}}: CS1 maint: multiple names: authors list (link) supplement
  3. ^ "Entrez Gene: PPARGC1A peroxisome proliferator-activated receptor gamma, coactivator 1 alpha".
  4. ^ Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, Eklund AC, Zhang-James Y, Kim PD, Hauser MA, Grünblatt E, Moran LB, Mandel SA, Riederer P, Miller RM, Federoff HJ, Wüllner U, Papapetropoulos S, Youdim MB, Cantuti-Castelvetri I, Young AB, Vance JM, Davis RL, Hedreen JC, Adler CH, Beach TG, Graeber MB, Middleton FA, Rochet JC, Scherzer CR (2010). "PGC-1{alpha}, A Potential Therapeutic Target for Early Intervention in Parkinson's Disease". Sci Transl Med. 2 (52): 52ra73. doi:10.1126/scitranslmed.3001059. PMID 20926834. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ a b Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM (1999). "Activation of PPARgamma coactivator-1 through transcription factor docking". Science. 286 (5443): 1368–71. doi:10.1126/science.286.5443.1368. PMID 10558993. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ, Edwards PA (2004). "Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) regulates triglyceride metabolism by activation of the nuclear receptor FXR". Genes Dev. 18 (2): 157–69. doi:10.1101/gad.1138104. PMC 324422. PMID 14729567. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A, Reed SI (2008). "SCFCdc4 acts antagonistically to the PGC-1α transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis". Genes Dev. 22 (2): 252–64. doi:10.1101/gad.1624208. PMC 2192758. PMID 18198341. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ a b c d e Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG (2003). "Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha". Mol. Cell. 12 (5): 1137–49. doi:10.1016/S1097-2765(03)00391-5. PMID 14636573. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999). "Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1". Cell. 98 (1): 115–24. doi:10.1016/S0092-8674(00)80611-X. PMID 10412986. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Delerive P, Wu Y, Burris TP, Chin WW, Suen CS (2002). "PGC-1 functions as a transcriptional coactivator for the retinoid X receptors". J. Biol. Chem. 277 (6): 3913–7. doi:10.1074/jbc.M109409200. PMID 11714715. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  11. ^ Wu, Yifei (2002). "Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1". J. Biol. Chem. 277 (11). United States: 8898–905. doi:10.1074/jbc.M110761200. ISSN 0021-9258. PMID 11751919. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link)

Further reading

Template:PBB Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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