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Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha
Identifiers
Symbols PPARGC1A; LEM6; PGC-1(alpha); PGC-1v; PGC1; PGC1A; PPARGC1
External IDs OMIM604517 MGI1342774 HomoloGene7485 GeneCards: PPARGC1A Gene
RNA expression pattern
PBB GE PPARGC1A 219195 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 10891 19017
Ensembl ENSG00000109819 ENSMUSG00000029167
UniProt Q9UBK2 Q3LIG0
RefSeq (mRNA) NM_013261 NM_008904
RefSeq (protein) NP_037393 NP_032930
Location (UCSC) Chr 4:
23.4 - 23.5 Mb
Chr 5:
51.75 - 51.84 Mb
PubMed search [1] [2]

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha is a protein that in humans is encoded by the PPARGC1A gene.[1] The protein encoded by this gene 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.[2]

Contents

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.

Interactions

PPARGC1A has been shown to interact with Thyroid hormone receptor beta,[3] MED17,[4] MED14,[4] CREB binding protein,[5] MED1,[4] Peroxisome proliferator-activated receptor gamma,[4][5] NRF1,[6] Nuclear receptor coactivator 1,[5] MED12,[4] Farnesoid X receptor,[7] FBXW7[8] and Retinoid X receptor alpha.[9]

See also

References

  1. ^ Esterbauer H, Oberkofler H, Krempler F, Patsch W (Feb 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.  
  2. ^ "Entrez Gene: PPARGC1A peroxisome proliferator-activated receptor gamma, coactivator 1 alpha". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10891.  
  3. ^ Wu, Yifei; Delerive Philippe, Chin William W, Burris Thomas P (Mar. 2002). "Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1". J. Biol. Chem. (United States) 277 (11): 8898–905. doi:10.1074/jbc.M110761200. ISSN 0021-9258. PMID 11751919.  
  4. ^ a b c d e Wallberg, Annika E; Yamamura Soichiro, Malik Sohail, Spiegelman Bruce M, Roeder Robert G (Nov. 2003). "Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha". Mol. Cell (United States) 12 (5): 1137–49. ISSN 1097-2765. PMID 14636573.  
  5. ^ a b c Puigserver, P; Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman B M (Nov. 1999). "Activation of PPARgamma coactivator-1 through transcription factor docking". Science (UNITED STATES) 286 (5443): 1368–71. ISSN 0036-8075. PMID 10558993.  
  6. ^ Wu, Z; Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla R C, Spiegelman B M (Jul. 1999). "Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1". Cell (UNITED STATES) 98 (1): 115–24. doi:10.1016/S0092-8674(00)80611-X. ISSN 0092-8674. PMID 10412986.  
  7. ^ Zhang, Yanqiao; Castellani Lawrence W, Sinal Christopher J, Gonzalez Frank J, Edwards Peter A (Jan. 2004). "Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR". Genes Dev. (United States) 18 (2): 157–69. doi:10.1101/gad.1138104. ISSN 0890-9369. PMID 14729567.  
  8. ^ Olson, Brian L; Hock M Benjamin, Ekholm-Reed Susanna, Wohlschlegel James A, Dev Kumlesh K, Kralli Anastasia, Reed Steven I (Jan. 2008). "SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis". Genes Dev. (United States) 22 (2): 252–64. doi:10.1101/gad.1624208. ISSN 0890-9369. PMID 18198341.  
  9. ^ Delerive, Philippe; Wu Yifei, Burris Thomas P, Chin William W, Suen Chen S (Feb. 2002). "PGC-1 functions as a transcriptional coactivator for the retinoid X receptors". J. Biol. Chem. (United States) 277 (6): 3913–7. doi:10.1074/jbc.M109409200. ISSN 0021-9258. PMID 11714715.  

External links

Further reading

  • Knutti D, Kralli A (2001). "PGC-1, a versatile coactivator.". Trends Endocrinol. Metab. 12 (8): 360–5. doi:10.1016/S1043-2760(01)00457-X. PMID 11551810.  
  • Puigserver P, Spiegelman BM (2003). "Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator.". Endocr. Rev. 24 (1): 78–90. doi:10.1210/er.2002-0012. PMID 12588810.  
  • Soyal S, Krempler F, Oberkofler H, Patsch W (2007). "PGC-1alpha: a potent transcriptional cofactor involved in the pathogenesis of type 2 diabetes.". Diabetologia 49 (7): 1477–88. doi:10.1007/s00125-006-0268-6. PMID 16752166.  
  • Handschin C, Spiegelman BM (2007). "Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism.". Endocr. Rev. 27 (7): 728–35. doi:10.1210/er.2006-0037. PMID 17018837.  
  • Liang H, Ward WF (2006). "PGC-1alpha: a key regulator of energy metabolism.". Advances in physiology education 30 (4): 145–51. doi:10.1152/advan.00052.2006. PMID 17108241.  

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

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