| First Author | Sano M | Year | 2007 |
| Journal | Cell Metab | Volume | 5 |
| Issue | 2 | Pages | 129-42 |
| PubMed ID | 17276355 | Mgi Jnum | J:129766 |
| Mgi Id | MGI:3770112 | Doi | 10.1016/j.cmet.2007.01.003 |
| Citation | Sano M, et al. (2007) Menage-a-trois 1 is critical for the transcriptional function of PPARgamma coactivator 1. Cell Metab 5(2):129-42 |
| abstractText | 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. |
