Phosphorylation of the histone deacetylase 7 modulates its stability and association with 14-3-3 proteins
Phosphorylation of the histone deacetylase 7 modulates its stability and association with 14-3-3 proteins
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DOI：
10.1074/jbc.m405179200
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发表时间：
2004-08-13
影响因子：
4.8
通讯作者：
Kao, HY
中科院分区：
文献类型：
--
作者：
Li, XF;Song, S;Kao, HY
II类组蛋白去乙酰化酶（HDAC）在肌生成中发挥作用，并抑制肌细胞增强因子2的转录激活。II类HDAC的一个显著特征是它们能够以细胞类型和信号依赖性方式在细胞核和细胞质之间穿梭。我们在这里证明，治疗与26 S蛋白酶体抑制剂，MG 132和ALLN，导致检测泛素化的HDAC 7，并导致积累的细胞质HDAC 7。我们还表明，用calyculin A（一种蛋白磷酸酶抑制剂）治疗，导致HDAC 7显著增加，但HDAC 5没有增加。HDAC 7的增加伴随着14-3-3蛋白与HDAC 7之间增强的相互作用。阻止与14-3-3蛋白相互作用的HDAC 7突变也阻断了calyculin A介导的稳定化。组成型活性钙/钙调蛋白依赖性激酶I的表达稳定HDAC 7，并导致HDAC 7和14-3-3之间的关联增加。总之，我们的研究结果表明，钙/钙调蛋白依赖性激酶I介导的HDAC 7磷酸化作用，部分地促进HDAC 7与14-3-3的结合并稳定HDAC 7。
Class II histone deacetylases (HDACs) play a role in myogenesis and inhibit transcriptional activation by myocyte enhancer factors 2. A distinct feature of class II HDACs is their ability to shuttle between the nucleus and the cytoplasm in a cell type- and signal-dependent manner. We demonstrate here that treatment with the 26 S proteosome inhibitors, MG132 and ALLN, leads to detection of ubiquitinated HDAC7 and causes accumulation of cytoplasmic HDAC7. We also show that treatment with calyculin A, a protein phosphatase inhibitor, leads to a marked increase of HDAC7 but not HDAC5. The increase in HDAC7 is accompanied by enhanced interaction between 14-3-3 proteins and HDAC7. HDAC7 mutations that prevent the interaction with 14-3-3 proteins also block calyculin A-mediated stabilization. Expression of constitutively active calcium/calmodulin-dependent kinase I stabilizes HDAC7 and causes an increased association between HDAC7 and 14-3-3. Together, our results suggest that calcium/calmodulin-dependent kinase I-mediated phosphorylation of HDAC7 acts, in part, to promote association of HDAC7 with 14-3-3 and stabilizes HDAC7.