Protein Kinase CK2 Regulates the Dimerization of Histone Deacetylase 1 (HDAC1) and HDAC2 during Mitosis
Protein Kinase CK2 Regulates the Dimerization of Histone Deacetylase 1 (HDAC1) and HDAC2 during Mitosis
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DOI：
10.1074/jbc.m112.440446
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发表时间：
2013-06-07
影响因子：
4.8
通讯作者：
Davie, James R.
中科院分区：
文献类型：
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作者：
Khan, Dilshad H.;He, Shihua;Davie, James R.
组蛋白去乙酰化酶1（HDAC 1）和HDAC 2是辅阻遏物复合物的组分，其通过调节动态蛋白乙酰化而参与染色质重塑和基因表达的调节。HDAC 1和HDAC 2形成同源和异源二聚体，其活性取决于二聚体的形成。间期细胞中HDAC 1和/或HDAC 2的磷酸化是HDAC辅阻遏物复合物形成所必需的。在这项研究中，我们发现在有丝分裂过程中，HDAC 2和HDAC 1磷酸化水平在较小程度上显著增加。当HDAC 1和-2在中期从染色体上移位时，它们彼此解离，但每种酶仍然与HDAC辅阻遏物复合物Sin 3、NuRD和CoREST的组分作为同源二聚体相关联。酶抑制研究和突变分析表明，蛋白激酶CK 2催化的HDAC 1和-2磷酸化对于这两种酶的解离至关重要。这些结果表明，辅阻遏物复合物，包括HDAC 1或HDAC 2同源二聚体，可能在有丝分裂过程中靶向不同的细胞蛋白。
Histone deacetylase 1 (HDAC1) and HDAC2 are components of corepressor complexes that are involved in chromatin remodeling and regulation of gene expression by regulating dynamic protein acetylation. HDAC1 and -2 form homo- and heterodimers, and their activity is dependent upon dimer formation. Phosphorylation of HDAC1 and/or HDAC2 in interphase cells is required for the formation of HDAC corepressor complexes. In this study, we show that during mitosis, HDAC2 and, to a lesser extent, HDAC1 phosphorylation levels dramatically increase. When HDAC1 and -2 are displaced from the chromosome during metaphase, they dissociate from each other, but each enzyme remains in association with components of the HDAC corepressor complexes Sin3, NuRD, and CoREST as homodimers. Enzyme inhibition studies and mutational analyses demonstrated that protein kinase CK2-catalyzed phosphorylation of HDAC1 and -2 is crucial for the dissociation of these two enzymes. These results suggest that corepressor complexes, including HDAC1 or HDAC2 homodimers, might target different cellular proteins during mitosis.