Choi S J, Park S Y, Han T H
Department of Molecular Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 300 Chunchundong, Jangangu, Suwon 440-746, Republic of Korea.
Nucleic Acids Res. 2001 Jul 1;29(13):2836-42. doi: 10.1093/nar/29.13.2836.
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.
肌细胞增强因子2(MEF2)蛋白属于转录因子的MADS盒家族,已发现四种MEF2蛋白,即MEF2A、MEF2B、MEF2C和MEF2D。MEF2蛋白已被证明在肌肉和神经组织的分化中起关键作用。MEF2蛋白的反式激活活性是如何被调控的,目前尚未完全了解。MEF2蛋白可被多种激酶激活,包括Erk5和钙/钙调蛋白依赖性激酶,并与包括组蛋白去乙酰化酶4和5(HDAC4和HDAC5)以及Cabin1在内的阻遏物相互作用。在研究MEF2活性调控的过程中,我们通过酵母双杂交筛选鉴定出14-3-3τ是一种与MEF2D相互作用的分子。我们发现14-3-3τ在体内与MEF2D形成复合物,并特异性增强MEF2的反式激活活性。瞬时转染和共沉淀实验结果表明,14-3-3τ通过竞争性抑制HDAC4与MEF2D的结合来激活MEF2D,从而影响肌肉细胞分化。