Histone Deacetylase 2 (HDAC2) Protein-dependent Deacetylation of Mortality Factor 4-like 1 (MORF4L1) Protein Enhances Its Homodimerization
Histone Deacetylase 2 (HDAC2) Protein-dependent Deacetylation of Mortality Factor 4-like 1 (MORF4L1) Protein Enhances Its Homodimerization
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死亡因子 4 样 1 (MORF4L1) 蛋白的组蛋白脱乙酰酶 2 (HDAC2) 蛋白依赖性脱乙酰作用增强其同二聚化
DOI：
10.1074/jbc.m113.527507
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发表时间：
2014-03-07
影响因子：
4.8
通讯作者：
Zou, Chunbin
中科院分区：
文献类型：
--
作者：
Chen, Yan;Li, Jin;Zou, Chunbin
背景：组蛋白乙酰转移酶MORF4L1形成同源二聚体执行其表观遗传功能，但其同源二聚的分子机制尚不清楚。结果：组蛋白去乙酰化酶HDAC2在Lys-148位上去乙酰化MORF4L1，促进MORF4L1同源二聚。结论：依赖HDAC2的MORF4L1去乙酰化促进了MORF4L1的同源二聚化，促进了复合体的形成，从而抑制了细胞的增殖。意义：MORF4L1同源二聚的分子控制可能影响细胞的基本过程，如增殖。组蛋白乙酰转移酶死亡因子4样1(MORF4L1)是一种相对较新的组蛋白乙酰转移酶组分，以同源二聚体的形式存在，发挥其表观遗传功能。MORF4L1的自组装机制尚不清楚。在这里，我们报告了Lys-148脱乙酰基对于促进MORF4L1自组装成同源二聚体单元是必不可少的。在MORF4L1的染色域和MORF4相关基因(MRG)结构域之间的NH2末端大约10个氨基酸中，Lys-148通常是乙酰化的。用精氨酸取代Lys-148可增强MORF4L1的自组装。然而，MORF4L1的乙酰化模拟产物，包括K148L和K148Q，取消了其组蛋白乙酰转移酶组分的自组装。HDAC2是一种脱乙酰酶，在Lys(148)处与MORF4L1相互作用并保持脱乙酰基状态，从而触发MORF4L1自组装。HDAC2的敲除降低了MORF4L1的自组装。依赖HDAC2的MORF4L1脱乙酰基促进了MORF4L1的同源二聚化，从而促进了复合体的形成以抑制细胞增殖。
Background: Histone acetyltransferase MORF4L1 forms a homodimer to perform its epigenetic function, but the molecular mechanisms for its homodimerization are unknown. Results: Histone deacetylase HDAC2 deacetylates MORF4L1 at Lys-148 to enhance MORF4L1 homodimerization. Conclusion: HDAC2-dependent deacetylation of MORF4L1 enhances MORF4L1 homodimerization, which facilitates complex formation to repress cellular proliferation. Significance: The molecular control of MORF4L1 homodimerization may impact fundamental cellular processes such as proliferation.Histone acetyltransferase mortality factor 4-like 1 (MORF4L1) is a relatively new histone acetyltransferase component that exists as a homodimer to exert its epigenetic function. The mechanism of MORF4L1 self-assembly is unknown. Here we report that Lys-148 deacetylation is indispensable for facilitating MORF4L1 self-assembly into a homodimeric unit. Among a stretch of approximate to 10 amino acids in the NH2 terminus between the chromodomain and MORF4-related gene (MRG) domain within MORF4L1, Lys-148 is normally acetylated. Substitution of Lys-148 with arginine augments MORF4L1 self-assembly. However, acetylation mimics of MORF4L1, including K148L and K148Q, abolished its self-assembly of the histone acetyltransferase component. HDAC2, a deacetylase, interacts with and keeps MORF4L1 in a deacetylation status at Lys(148) that triggers MORF4L1 self-assembly. Knockdown of HDAC2 reduces MORF4L1 self-assembly. HDAC2-dependent deacetylation of MORF4L1 enhances MORF4L1 homodimerization, thus facilitating the functionality of complex formation to repress cell proliferation.