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J Biol Chem. 2008 Dec 26;283(52):36154-67. doi: 10.1074/jbc.M807461200. Epub 2008 Oct 31.

Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype.

Author information

1
Department of Biochemistry, School of Medicine, University of Missouri, Columbia, Missouri 65211, USA. tsikar@missouri.edu

Abstract

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 (Vmax), 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.

PMID:
18978355
PMCID:
PMC2606011
DOI:
10.1074/jbc.M807461200
[Indexed for MEDLINE]
Free PMC Article

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