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

Myocyte enhancer binding factor 2 (MEF2) proteins belong to the MADS box fa mily of transcription factors and four MEF2 proteins, MEF2A, MEF2B, MEF2C a nd MEF2D, have been found. MEF2 proteins have been shown to play critical r oles in differentiation of muscles and neuronal tissues. How transactivatio nal activity of MEF2 proteins is regulated is not fully understood. MEF2 pr oteins are activated by several kinases, including Erk5 and calcium/calmodu lin-dependent kinase, and interact with repressors, including histone deace tylases 4 and 5 (HDAC4 and HDAC5) and Cabin1, During the effort to understa nd regulation of MEF2 activity, we identified 14-3-3 tau as a MEF2D-interac ting molecule by yeast two-hybrid screening. We found that 14-3-3 tau forms a complex with MEF2D in vivo and specifically enhances MEF2 transactivatio nal activity. The results from transient transfection and co-precipitation experiments suggest that 14-3-3 tau activates MEF2D by competitively inhibi ting HDAC4 from binding to MEF2D and thereby affects muscle cell differenti ation.