| First Author | Tsika RW | Year | 2008 |
| Journal | J Biol Chem | Volume | 283 |
| Issue | 52 | Pages | 36154-67 |
| PubMed ID | 18978355 | Mgi Jnum | J:143917 |
| Mgi Id | MGI:3829334 | Doi | 10.1074/jbc.M807461200 |
| Citation | Tsika RW, et al. (2008) Overexpression of TEAD-1 in Transgenic Mouse Striated Muscles Produces a Slower Skeletal Muscle Contractile Phenotype. J Biol Chem 283(52):36154-67 |
| abstractText | TEA domain (TEAD) transcription factors serve important functional roles during embryonic development and in striated muscle gene expression. Our previous work has implicated a role for TEAD-1 in the fast-to-slow fiber-type transition in response to mechanical overload. To investigate whether TEAD-1 is a modulator of slow muscle gene expression in vivo, we developed transgenic mice expressing hemagglutinin (HA)-tagged TEAD-1 under the control of the muscle creatine kinase promoter. We show that striated muscle-restricted HA-TEAD-1 expression induced a transition toward a slow muscle contractile protein phenotype, slower shortening velocity (V(max)), and longer contraction and relaxation times in adult fast twitch extensor digitalis longus muscle. Notably, HA-TEAD-1 overexpression resulted in an unexpected activation of GSK-3alpha/beta and decreased nuclear beta-catenin and NFATc1/c3 protein. These effects could be reversed in vivo by mechanical overload, which decreased muscle creatine kinase-driven TEAD-1 transgene expression, and in cultured satellite cells by TEAD-1-specific small interfering RNA. These novel in vivo data support a role for TEAD-1 in modulating slow muscle gene expression. |
