14-3-3tau associates with and activates the MEF2D transcription factor during muscle cell differentiation

Myocyte enhancer binding factor 2 (MEF2) proteins belong to the MADS box family of transcription factors and four MEF2 proteins, MEF2A, MEF2B, MEF2C and MEF2D, have been found. MEF2 proteins have been shown to play critical roles in differentiation of muscles and neuronal tissues. How transactivational activity of MEF2 proteins is regulated is not fully understood. MEF2 proteins are activated by several kinases, including Erk5 and calcium/calmodulin-dependent kinase, and interact with repressors, including histone deacetylases 4 and 5 (HDAC4 and HDAC5) and Cabin1. During the effort to understand regulation of MEF2 activity, we identified 14-3-3tau as a MEF2D-interacting molecule by yeast two-hybrid screening. We found that 14-3-3tau forms a complex with MEF2D in vivo and specifically enhances MEF2 transactivational activity. The results from transient transfection and co-precipitation experiments suggest that 14-3-3tau activates MEF2D by competitively inhibiting HDAC4 from binding to MEF2D and thereby affects muscle cell differentiation.