| pubmed-article:18198341 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18198341 | lifeskim:mentions | umls-concept:C1336776 | lld:lifeskim |
| pubmed-article:18198341 | lifeskim:mentions | umls-concept:C1519749 | lld:lifeskim |
| pubmed-article:18198341 | lifeskim:mentions | umls-concept:C0599894 | lld:lifeskim |
| pubmed-article:18198341 | lifeskim:mentions | umls-concept:C1551336 | lld:lifeskim |
| pubmed-article:18198341 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:18198341 | pubmed:dateCreated | 2008-1-16 | lld:pubmed |
| pubmed-article:18198341 | pubmed:abstractText | Peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) is a highly regulated transcriptional coactivator that coordinates energy metabolism in mammals. Misregulation of PGC-1alpha has been implicated in the pathogenesis of several human diseases, including diabetes, obesity, and neurological disorders. We identified SCF(Cdc4) as an E3 ubiquitin ligase that regulates PGC-1alpha through ubiquitin-mediated proteolysis. PGC-1alpha contains two Cdc4 phosphodegrons that bind Cdc4 when phosphorylated by Glycogen Synthase Kinase 3beta (GSK3beta) and p38 MAPK, leading to SCF(Cdc4)-dependent ubiquitylation and proteasomal degradation of PGC-1alpha. Furthermore, SCF(Cdc4) negatively regulates PGC-1alpha-dependent transcription. We demonstrate that RNAi-mediated reduction of Cdc4 in primary neurons results in an increase of endogenous PGC-1alpha protein, while ectopic expression of Cdc4 leads to a reduction of endogenous PGC-1alpha protein. Finally, under conditions of oxidative stress in neurons, Cdc4 levels are decreased, leading to an increase in PGC-1alpha protein and PGC-1alpha-dependent transcription. These results suggest that attenuation of SCF(Cdc4)-dependent proteasomal degradation of PGC-1alpha has a role in mediating the PGC-1alpha-dependent transcriptional response to oxidative stress. | lld:pubmed |
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| pubmed-article:18198341 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18198341 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18198341 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18198341 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:18198341 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18198341 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:18198341 | pubmed:issn | 0890-9369 | lld:pubmed |
| pubmed-article:18198341 | pubmed:author | pubmed-author:KralliAnastas... | lld:pubmed |
| pubmed-article:18198341 | pubmed:author | pubmed-author:WohlschlegelJ... | lld:pubmed |
| pubmed-article:18198341 | pubmed:author | pubmed-author:DevKumlesh... | lld:pubmed |
| pubmed-article:18198341 | pubmed:author | pubmed-author:ReedSteven... | lld:pubmed |
| pubmed-article:18198341 | pubmed:author | pubmed-author:Ekholm-ReedSu... | lld:pubmed |
| pubmed-article:18198341 | pubmed:author | pubmed-author:HockM... | lld:pubmed |
| pubmed-article:18198341 | pubmed:author | pubmed-author:OlsonBrian... | lld:pubmed |
| pubmed-article:18198341 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:18198341 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:18198341 | pubmed:volume | 22 | lld:pubmed |
| pubmed-article:18198341 | pubmed:owner | NLM | lld:pubmed |
