14-3-3依赖的细胞定位对组蛋白去乙酰化酶4和5及转录活性的调控
Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization.
作者信息
Grozinger C M, Schreiber S L
机构信息
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
出版信息
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7835-40. doi: 10.1073/pnas.140199597.
Transcription is controlled in part by the dynamic acetylation and deacetylation of histone proteins. The latter process is mediated by histone deacetylases (HDACs). Previous analysis of the regulation of HDAC activity in transcription has focused primarily on the recruitment of HDAC proteins to specific promoters or chromosomal domains by association with DNA-binding proteins. To characterize the cellular function of the recently identified HDAC4 and HDAC5 proteins, complexes were isolated by immunoprecipitation. Both HDACs were found to interact with14-3-3 proteins at three phosphorylation sites. The association of 14-3-3 with HDAC4 and HDAC5 results in the sequestration of these proteins in the cytoplasm. Loss of this interaction allows HDAC4 and HDAC5 to translocate to the nucleus, interact with HDAC3, and repress gene expression. Regulation of the cellular localization of HDAC4 and HDAC5 by 14-3-3 represents a mechanism for controlling the transcriptional activity of these class II HDAC proteins.
转录部分受组蛋白的动态乙酰化和去乙酰化调控。后一过程由组蛋白去乙酰化酶（HDACs）介导。先前对转录过程中HDAC活性调控的分析主要集中在通过与DNA结合蛋白结合，将HDAC蛋白招募到特定启动子或染色体结构域。为了表征最近鉴定出的HDAC4和HDAC5蛋白的细胞功能，通过免疫沉淀分离复合物。发现这两种HDAC在三个磷酸化位点与14-3-3蛋白相互作用。14-3-3与HDAC4和HDAC5的结合导致这些蛋白在细胞质中隔离。这种相互作用的丧失使HDAC4和HDAC5易位至细胞核，与HDAC3相互作用，并抑制基因表达。14-3-3对HDAC4和HDAC5细胞定位的调控代表了一种控制这些II类HDAC蛋白转录活性的机制。
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