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组蛋白去乙酰化酶相关的 Sin3B 蛋白抑制 DREAM 复合物靶标,并与 APC/C 合作促进静止。

The HDAC-Associated Sin3B Protein Represses DREAM Complex Targets and Cooperates with APC/C to Promote Quiescence.

机构信息

Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, NY 10016, USA.

Department of Internal Medicine and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

出版信息

Cell Rep. 2018 Dec 4;25(10):2797-2807.e8. doi: 10.1016/j.celrep.2018.11.024.

Abstract

The mammalian DREAM complex is responsible for the transcriptional repression of hundreds of cell-cycle-related genes in quiescence. How the DREAM complex recruits chromatin-modifying entities to aid in its repression remains unknown. Using unbiased proteomics analysis, we have uncovered a robust association between the chromatin-associated Sin3B protein and the DREAM complex. We have determined that genetic inactivation of Sin3B results in the de-repression of DREAM target genes during quiescence but is insufficient to allow quiescent cells to resume proliferation. However, inactivation of APC/C was sufficient for Sin3B cells, but not parental cells, to re-enter the cell cycle. These studies identify Sin3B as a transcriptional corepressor associated with the DREAM complex in quiescence and reveals a functional cooperation between E2F target repression and APC/C in the negative regulation of cell-cycle progression.

摘要

哺乳动物的 DREAM 复合物负责在静止期转录抑制数百个细胞周期相关基因。DREAM 复合物如何招募染色质修饰因子来帮助其抑制仍然未知。使用无偏proteomics 分析,我们已经发现染色质相关的 Sin3B 蛋白与 DREAM 复合物之间存在强大的关联。我们已经确定,Sin3B 的遗传失活导致静止期 DREAM 靶基因的去抑制,但不足以使静止细胞重新开始增殖。然而,APC/C 的失活足以使 Sin3B 细胞而不是亲本细胞重新进入细胞周期。这些研究表明 Sin3B 是静止期与 DREAM 复合物相关的转录共抑制因子,并揭示了 E2F 靶基因抑制与 APC/C 在细胞周期进程负调控中的功能合作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f9/6324198/e2646b314794/nihms-1516646-f0002.jpg

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