Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 230, Issue 10, Pages 2330-2336Publisher
WILEY
DOI: 10.1002/jcp.24978
Keywords
-
Categories
Funding
- The American Heart Association Fellowship (AHA) [AHA-0726015T, R01 CA163336, RO1-AR043369, P01 CA163222, R01 HL094499]
- PhRMA Foundation
- National Cancer Institute
- Melanoma Research Alliance
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- National Institutes of Health
- US-Israel Binational Science Foundation
- Doris Duke Medical Research Foundation
Ask authors/readers for more resources
The microphthalmia (MiT) family of transcription factors is an important mediator of metabolism. Family members Mitf and Tfeb directly regulate the expression of the master regulator of metabolism, peroxisome-proliferator activated receptor gamma coactivator-1 alpha (Pgc-1alpha), in melanomas and in the liver, respectively. Pgc-1alpha is enriched in tissues with high oxidative capacity and plays an important role in the regulation of mitochondrial biogenesis and cellular metabolism. In skeletal muscle, Pgc-1alpha affects many aspects of muscle functionally such as endurance, fiber-type switching, and insulin sensitivity. Tfe3 also regulates muscle metabolic genes that enhance insulin sensitivity in skeletal muscle. Tfe3 has not yet been shown to regulate Pgc-1alpha expression. Our results reported here show that Tfe3 directly regulates Pgc-1alpha expression in myotubes. Tfe3 ectopic expression induces Pgc-1alpha, and Tfe3 silencing suppresses Pgc-1alpha expression. This regulation is direct, as shown by Tfe3's binding to E-boxes on the Pgc-1alpha proximal promoter. We conclude that Tfe3 is a critical transcription factor that regulates Pgc-1alpha gene expression in myotubes. Since Pgc-1alpha coactivates numerous biological programs in diverse tissues, the regulation of its expression by upstream transcription factors such Tfe3 implies potential opportunities for the treatment of diseases where modulation of Pgc-1alpha expression may have important clinical outcomes. (C) 2015 Wiley Periodicals, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available