Menage-a-trois 1 is critical for the transcriptional function of PPAR gamma coactivator 1

作者：Sano Motoaki; Izumi Yasukatsu; Helenius Katja; Asakura Masanori; Rossi Derrick J; Xie Min; Taffet George; Hu Lingyun; Pautler Robia G; Wilson Christopher R; Boudina Sihem; Abel E Dale; Taegtmeyer Heinrich; Scaglia Fernando; Graham Brett H; Kralli Anastasia; Shimizu Noriaki; Tanaka Hirotoshi; Makela Tomi P; Schneider Michael D^*

来源：Cell Metabolism, 2007, 5(2): 129-142.

DOI：10.1016/j.cmet.2007.01.003

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-1 alpha failed to activate PGC-1-responsive promoters and nuclear receptors, GAL4-PGC-1 alpha was functionally defective, and PGC-1 beta 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.

• 出版日期2007-2
• 单位河北医科大学