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Regulation of the Transcriptional Coactivator PGC-1 via MAPK-Sensitive Interaction with a Repressor

Darko Knutti, Dieter Kressler and Anastasia Kralli
Proceedings of the National Academy of Sciences of the United States of America
Vol. 98, No. 17 (Aug. 14, 2001), pp. 9713-9718
Stable URL: http://www.jstor.org/stable/3056418
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Regulation of the Transcriptional Coactivator PGC-1 via MAPK-Sensitive Interaction with a Repressor
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Abstract

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.

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