Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor

D. Knutti, D. Kressler, A. Kralli

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)9713-9718
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number17
DOIs
StatePublished - Aug 14 2001

ASJC Scopus subject areas

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