Direct Interaction between Myocyte Enhancer Factor 2 (MEF2) and Protein Phosphatase 1 alpha Represses MEF2-Dependent Gene Expression

作者：Perry R L S; Yang C; Soora N; Salma J; Marback M; Naghibi L; Ilyas H; Chan J; Gordon J W; McDermott J C^*

来源：Molecular and Cellular Biology, 2009, 29(12): 3355-3366.

DOI：10.1128/MCB.00227-08

The myocyte enhancer factor 2 (MEF2) transcription factors play important roles in neuronal, cardiac, and skeletal muscle tissues. MEF2 serves as a nuclear sensor, integrating signals from several signaling cascades through protein-protein interactions with kinases, chromatin remodeling factors, and other transcriptional regulators. Here, we report a novel interaction between the catalytic subunit of protein phosphatase 1 alpha (PP1 alpha) and MEF2. Interaction occurs within the nucleus, and binding of PP1 alpha to MEF2 potently represses MEF2-dependent transcription. The interaction utilizes uncharacterized domains in both PP1 alpha and MEF2, and PP1 alpha phosphatase activity is not obligatory for MEF2 repression. Moreover, a MEF2-PP1 alpha regulatory complex leads to nuclear retention and recruitment of histone deacetylase 4 to MEF2 transcription complexes. PP1 alpha-mediated repression of MEF2 overrides the positive influence of calcineurin signaling, suggesting PP1 alpha exerts a dominant level of control over MEF2 function. Indeed, PP1 alpha-mediated repression of MEF2 function interferes with the prosurvival effect of MEF2 in primary hippocampal neurons. The PP1 alpha-MEF2 interaction constitutes a potent locus of control for MEF2-dependent gene expression, having potentially important implications for neuronal cell survival, cardiac remodeling in disease, and terminal differentiation of vascular, cardiac, and skeletal muscle.

• 出版日期2009-6-15