Direct interaction of Ca2+/calmodulin inhibits histone deacetylase 5 repressor core binding to myocyte enhancer factor 2
Direct interaction of Ca2+/calmodulin inhibits histone deacetylase 5 repressor core binding to myocyte enhancer factor 2
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DOI：
10.1074/jbc.m301646200
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发表时间：
2003-05-16
影响因子：
4.8
通讯作者：
Richmond, TJ
中科院分区：
文献类型：
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作者：
Berger, I;Bieniossek, C;Richmond, TJ
肌细胞增强因子2(MEF2)蛋白在心肌和骨骼肌细胞分化中起着关键作用。MEF2因子受组蛋白脱乙酰酶5(HDAC5)等组蛋白脱乙酰酶的调控。HDAC5反过来对细胞内钙感受器钙调蛋白介导的钙信号作出反应。在这里，结合蛋白质分解、基质辅助激光解吸电离质谱仪、Edman降解、圆二色谱、凝胶过滤和表面等离子体共振研究来定义和表征HDAC5的稳定核心区，并检测其与MEF2a和钙调蛋白的相互作用。实时结合实验的结果为钙/钙调蛋白与HDAC5的直接相互作用提供了证据，从而抑制了MEF2a与该酶的结合。
Myocyte enhancer factor 2 (MEF2) proteins play a pivotal role in the differentiation of cardiac and skeletal muscle cells. MEF2 factors are regulated by histone deacetylase enzymes such as histone deacetylase 5 (HDAC5). HDAC5 in turn is responsive to Ca2+ signaling mediated by the intracellular calcium sensor calmodulin. Here a combination of proteolytic fragmentation, matrix-assisted laser desorption ionization mass spectrometry, Edman degradation, circular dichroism, gel filtration, and surface plasmon resonance studies is utilized to define and characterize a stable core domain of HDAC5 and to examine its interactions with MEF2a and calmodulin. Results from real time binding experiments provide evidence for direct interaction of Ca2+/calmodulin with HDAC5 inhibiting MEF2a association with this enzyme.