Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family
Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family
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DOI：
10.1074/jbc.m111871200
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发表时间：
2002-07-12
影响因子：
4.8
通讯作者：
Atadja, P
中科院分区：
文献类型：
--
作者：
Gao, L;Cueto, MA;Atadja, P
我们已经克隆并鉴定了属于组蛋白去乙酰化酶家族的人cDNA，我们将其命名为HDAC11。预测的HDAC 11氨基酸序列揭示了347个残基的开放阅读框架，相应的分子量为39 kDa。推定的HDAC11蛋白的序列分析表明，它含有保守的残基，在催化核心区域共享的I类和11哺乳动物HDAC酶。HDAC 11的推定直向同源物存在于灵长类动物、小鼠、果蝇和植物中。表位标记的HDAC11蛋白在哺乳动物细胞中表达显示组蛋白脱乙酰酶活性。此外，HDAC 11的酶活性被已知的组蛋白脱乙酰酶抑制剂trapoxin抑制。多组织北方印迹和实时荧光PCR实验表明，HDAC 11转录本的高表达水平仅限于肾脏、心脏、脑、骨骼肌和睾丸。表位标记的HDAC11蛋白主要定位于细胞核。免疫共沉淀实验表明，HDAC11可能存在于也含有HDAC6的蛋白质复合物中。这些结果表明，HDAC11是一个新的和独特的组蛋白去乙酰化酶家族的成员，它可能有不同的生理功能，从那些已知的HDACs。
We have cloned and characterized a human cDNA that belongs to the histone deacetylase family, which we designate as HDAC11. The predicted HDAC11 amino acid sequence reveals an open reading frame of 347 residues with a corresponding molecular mass of 39 kDa. Sequence analyses of the putative HDAC11 protein indicate that it contains conserved residues in the catalytic core regions shared by both class I and 11 mammalian HDAC enzymes. Putative orthologues of HDAC11 exist in primate, mouse, Drosophila, and plant. Epitope-tagged HDAC11 protein expressed in mammalian cells displays histone deacetylase activity in vitro. Furthermore, HDAC11's enzymatic activity is inhibited by trapoxin, a known histone deacetylase inhibitor. Multiple tissue Northern blot and real-time PCR experiments show that the high expression level of HDAC11 transcripts is limited to kidney, heart, brain,, skeletal muscle, and testis. Epitope-tagged HDAC11 protein localizes predominantly to the cell nucleus. Co-immunoprecipitation experiments indicate that HDAC11 may be present in protein complexes that also contain HDAC6. These results indicate that HDAC11 is a novel and unique member of the histone deacetylase family and it may have distinct physiological roles from those of the known HDACs.