Ménage-à-Trois 1 Is Critical for the Transcriptional Function of PPARγ Coactivator 1

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

doi:10.1016/j.cmet.2007.01.003

Back

Ménage-à-Trois 1 Is Critical for the Transcriptional Function of PPARγ Coactivator 1

Journal article

Open access

Peer reviewed

Ménage-à-Trois 1 Is Critical for the Transcriptional Function of PPARγ Coactivator 1

Motoaki Sano, Yasukatsu Izumi, Katja Helenius, Masanori Asakura, Derrick J Rossi, Min Xie, George Taffet, Lingyun Hu, Robia G Pautler, Christopher R Wilson, …

Cell metabolism, Vol.5(2), pp.129-142

02/07/2007

DOI: 10.1016/j.cmet.2007.01.003

PMID: 17276355

Files and links (1)

url

https://doi.org/10.1016/j.cmet.2007.01.003View

Published (Version of record) Open Access

Abstract

The Cdk7/cyclin H/ménage-à-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 γ 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-1α failed to activate PGC-1-responsive promoters and nuclear receptors, GAL4-PGC-1α was functionally defective, and PGC-1β 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.

HUMDISEASE

Details

Title: Subtitle: Ménage-à-Trois 1 Is Critical for the Transcriptional Function of PPARγ Coactivator 1
Creators: Motoaki Sano - Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA
Yasukatsu Izumi - Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA
Katja Helenius - Molecular Cancer Biology Program & Institute of Biomedicine, Biomedicum Helsinki, 00014 University of Helsinki, Finland
Masanori Asakura - Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA
Derrick J Rossi - Molecular Cancer Biology Program & Institute of Biomedicine, Biomedicum Helsinki, 00014 University of Helsinki, Finland
Min Xie - Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA
George Taffet - Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
Lingyun Hu - Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
Robia G Pautler - Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
Christopher R Wilson - Department of Internal Medicine, University of Texas–Houston Medical School, Houston, TX 77030, USA
Sihem Boudina - Program in Human Molecular Biology & Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
E. Dale Abel - Program in Human Molecular Biology & Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Heinrich Taegtmeyer - Department of Internal Medicine, University of Texas–Houston Medical School, Houston, TX 77030, USA
Fernando Scaglia - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Brett H Graham - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Anastasia Kralli - Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Noriaki Shimizu - Division of Clinical Immunology and Department of Rheumatology and Allergy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Hirotoshi Tanaka - Division of Clinical Immunology and Department of Rheumatology and Allergy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Tomi P Mäkelä - Molecular Cancer Biology Program & Institute of Biomedicine, Biomedicum Helsinki, 00014 University of Helsinki, Finland
Michael D Schneider - Center for Cardiovascular Development, Baylor College of Medicine, Houston, TX 77030, USA
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.5(2), pp.129-142
Publisher: Elsevier Inc
DOI: 10.1016/j.cmet.2007.01.003
PMID: 17276355
ISSN: 1550-4131
eISSN: 1932-7420
Language: English
Date published: 02/07/2007
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024507802771

Metrics

25 Record Views

52 Times Cited - Web of Science