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"Menage-a-trois 1 is critical for the transcriptional function of PPARgamma coactivator 1." |
Sano M, Izumi Y, Helenius K, Asakura M, Rossi DJ, Xie M, Taffet G, Hu L, Pautler RG, Wilson CR, Boudina S, Abel ED, Taegtmeyer H, Scaglia F, Graham BH, Kralli A, Shimizu N, Tanaka H, Makela TP, Schneider MD |
Published Jan. 1, 2007 in Cell Metab volume 5 .
Pubmed ID: 17276355
Abstract:
| The Cdk7/cyclin H/menage-a-trois 1 (MAT1) heterotrimer has proposed functions in transcription as the kinase component of basal transcription factor TFIIH and is activated in adult hearts by Gq-, calcineurin-, and biomechanical stress-dependent pathways for hypertrophic growth. Using cardiac-specific Cre, we have ablated MAT1 in myocardium. Despite reduced Cdk7 activity, MAT1-deficient hearts grew normally, but fatal heart failure ensued at 6-8 weeks. By microarray profiling, quantitative RT-PCR, and western blotting at 4 weeks, genes for energy metabolism were found to be suppressed selectively, including targets of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1). Cardiac metabolic defects were substantiated in isolated perfused hearts and isolated mitochondria. In culture, deleting MAT1 with Cre disrupted PGC-1 function: PGC-1alpha failed to activate PGC-1-responsive promoters and nuclear receptors, GAL4-PGC-1alpha was functionally defective, and PGC-1beta was likewise deficient. PGC-1 bound to both MAT1 and Cdk7 in coprecipitation assays. Thus, we demonstrate a requirement for MAT1 in the operation of PGC-1 coactivators that control cell metabolism. |
This publication refers to following REPAIRtoire entries:
| Genes |
Last modification of this entry: Oct. 6, 2010
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