Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor.
Mechanisms and signals that regulate transcriptional coactivators are still largely unknown. Here we provide genetic evidence for a repressor that interacts with and regulates the nuclear receptor coactivator PGC-1. Association with the repressor requires a PGC-1 protein interface that is similar to the one used by nuclear receptors. Removal of the repressor enhances PGC-1 coactivation of steroid hormone responses. We also provide evidence that interaction of the repressor with PGC-1 is regulated by mitogen-activated protein kinase ( MAPK) signaling. Activation of the MAPK p38 enhances the activity of wild-type PGC-1 but not of a PGC-1 variant that no longer interacts with the repressor. Finally, p38 activation enhances steroid hormone response in a PGC-1-dependent manner. Our data suggest a model where the repressor and nuclear receptors compete for recruiting PGC-1 to an inactive and active state, respectively. Extracellular signals such as nuclear receptor ligands or activators of the MAPK p38 can shift the equilibrium between the two states.[1]References
- Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor. Knutti, D., Kressler, D., Kralli, A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
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