Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex
Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex
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DOI：
10.1101/gad.1037502
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发表时间：
2002-12-15
影响因子：
10.5
通讯作者：
Lazar, MA
中科院分区：
文献类型：
--
作者：
Guenther, MG;Yu, JJ;Lazar, MA
历史尾的乙酰化是基因活性的主要决定因素。组蛋白去乙酰化酶3 （HDAC3）的活性需要核受体辅助抑制因子SMRT。在这里，我们报道了HDAC3只有在包括TCP-1环复合物（TRiC）在内的细胞伴侣启动后才能与SMRT相互作用，这是在atp依赖过程中HDAC3正确折叠所必需的。SMRT取代HDAC3中的TRiC，产生一种活性HDAC酶。因此，SMRT-HDAC3抑制复合体加入了VHL-elongin BC肿瘤抑制复合体和周期蛋白E-Cdk2细胞周期调节复合体，成为需要TRiC才能正常组装和发挥功能的关键细胞机器。HDAC3活性的严格控制强调了组蛋白去乙酰化仅发生在基因组的目标区域的细胞必要性。
The acetylation of historic tails is a primary determinant of gene activity. Histone deacetylase 3 (HDAC3) requires the nuclear receptor corepressor SMRT for HDAC enzyme activity. Here we report that HDAC3 interacts with SMRT only after priming by cellular chaperones including the TCP-1 ring complex (TRiC), which is required for proper folding of HDAC3 in an ATP-dependent process. SMRT displaces TRiC from HDAC3, yielding an active HDAC enzyme. The SMRT-HDAC3 repression complex thus joins the VHL-elongin BC tumor suppression complex and the cyclin E-Cdk2 cell cycle regulation complex as critical cellular machines requiring TRiC for proper assembly and function. The strict control of HDAC3 activity underscores the cellular imperative that histone deacetylation occur only in targeted regions of the genome.