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多梳蛋白复合物蛋白 PSC 在细胞周期调控中的转录非依赖性功能。

Transcription-independent function of Polycomb group protein PSC in cell cycle control.

机构信息

Department of Biochemistry and Centre for Biomedical Genetics, Erasmus University Medical Centre, Post Office Box 1738, 3000 DR, Rotterdam, Netherlands.

出版信息

Science. 2012 May 11;336(6082):744-7. doi: 10.1126/science.1215927. Epub 2012 Apr 5.

Abstract

Polycomb group (PcG) proteins control development and cell proliferation through chromatin-mediated transcriptional repression. We describe a transcription-independent function for PcG protein Posterior sex combs (PSC) in regulating the destruction of cyclin B (CYC-B). A substantial portion of PSC was found outside canonical PcG complexes, instead associated with CYC-B and the anaphase-promoting complex (APC). Cell-based experiments and reconstituted reactions established that PSC and Lemming (LMG, also called APC11) associate and ubiquitylate CYC-B cooperatively, marking it for proteosomal degradation. Thus, PSC appears to mediate both developmental gene silencing and posttranslational control of mitosis. Direct regulation of cell cycle progression might be a crucial part of the PcG system's function in development and cancer.

摘要

多梳抑制复合物(PcG)蛋白通过染色质介导的转录抑制来控制发育和细胞增殖。我们描述了 PcG 蛋白 Posterior sex combs(PSC)在调节细胞周期蛋白 B(CYC-B)降解中的一个转录非依赖性功能。大量 PSC 被发现位于典型 PcG 复合物之外,而是与 CYC-B 和后期促进复合物(APC)相关联。基于细胞的实验和重建反应确立了 PSC 和 Lemming(LMG,也称为 APC11)相互作用并协同泛素化 CYC-B,将其标记为蛋白酶体降解。因此,PSC 似乎介导了发育基因沉默和有丝分裂后翻译控制。细胞周期进程的直接调控可能是 PcG 系统在发育和癌症中的功能的关键部分。

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