Department of Biochemistry and Centre for Biomedical Genetics, Erasmus University Medical Centre, Post Office Box 1738, 3000 DR, Rotterdam, Netherlands.
Science. 2012 May 11;336(6082):744-7. doi: 10.1126/science.1215927. Epub 2012 Apr 5.
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.
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。