Activation of nuclear receptor coactivator PGC-1alpha by arginine methylation.
Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), a tissue-specific and inducible transcriptional coactivator for several nuclear receptors, plays a key role in energy metabolism. We report here that PGC-1alpha coactivator activity is potentiated by arginine methylation by protein arginine methyltransferase 1 (PRMT1), another nuclear receptor coactivator. Mutation of three substrate arginines in the C-terminal region of PGC-1alpha abolished the cooperative coactivator function of PGC-1alpha and PRMT1, and compromised the ability of PGC-1alpha to induce endogenous target genes. Finally, endogenous PRMT1 contributes to PGC-1alpha coactivator activity, and to the induction of genes important for mitochondrial biogenesis.
Teyssier
Catherine
C
Department of Pathology, University of Southern California, Los Angeles, California 90089, USA.
Ma
Han
H
Emter
Roger
R
Kralli
Anastasia
A
Stallcup
Michael R
MR
D000818:Animals; D001120:Arginine / Q000737:chemistry; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008745:Methylation; D016297:Mutagenesis, Site-Directed; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011994:Recombinant Proteins; D014157:Transcription Factors; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases