The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
SCFCdc4 acts antagonistically to the PGC-1α transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis
Open accessAbstract
Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a highly regulated transcriptional coactivator that coordinates energy metabolism in mammals. Misregulation of PGC-1α 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-1α through ubiquitin-mediated proteolysis. PGC-1α contains two Cdc4 phosphodegrons that bind Cdc4 when phosphorylated by Glycogen Synthase Kinase 3β (GSK3β) and p38 MAPK, leading to SCF Cdc4-dependent ubiquitylation and proteasomal degradation of PGC-1α. Furthermore, SCF Cdc4 negatively regulates PGC-1α-dependent transcription. We demonstrate that RNAi-mediated reduction of Cdc4 in primary neurons results in an increase of endogenous PGC-1α protein, while ectopic expression of Cdc4 leads to a reduction of endogenous PGC-1α protein. Finally, under conditions of oxidative stress in neurons, Cdc4 levels are decreased, leading to an increase in PGC-1α protein and PGC-1α-dependent transcription. These results suggest that attenuation of SCF Cdc4-dependent proteasomal degradation of PGC-1α has a role in mediating the PGC-1α-dependent transcriptional response to oxidative stress.
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Lysine Acetylation: Codified Crosstalk with Other Posttranslational Modifications
Yang, X.-J., & Seto, E. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.07.002 · Cited by 1,006
Little, J. P., Safdar, A., Wilkin, G. P., Tarnopolsky, M. A., & Gibala, M. J. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2009.181743 · Cited by 667
Transcriptional Control of Mitochondrial Biogenesis and Function
Hock, M. B., & Kralli, A. (2009) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163119 · Cited by 614
Self-citationAustin, S., & St-Pierre, J. (2012) · Journal of Cell Science · doi:10.1242/jcs.113662 · Cited by 608
Metadata
- Authors
- Olson, B. L., Hock, M. B., Ekholm-Reed, S., Wohlschlegel, J. A., Dev, K. K., Kralli, A., & Reed, S. I.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-01-15
- Volume
- 22
- Issue
- 2
- Pages
- 252-264
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2135150182
- Cited by
- 185
- References
- 15
- Type
- posted content
- Language
- en
- Open access
- diamond
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- The paper
- Olson, B. L., Hock, M. B., Ekholm-Reed, S., Wohlschlegel, J. A., Dev, K. K., Kralli, A., & Reed, S. I. (2008). SCFCdc4 acts antagonistically to the PGC-1α transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis. Genes & Development. https://doi.org/10.1101/gad.1624208
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