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The DREAM complex through its subunit Lin37 cooperates with Rb to initiate quiescence
eLife ( IF 6.4 ) Pub Date : 2017-09-18 , DOI: 10.7554/elife.26876
Christina FS Mages 1 , Axel Wintsche 1, 2 , Stephan H Bernhart 3, 4 , Gerd A Müller 1
Affiliation  

The retinoblastoma Rb protein is an important factor controlling the cell cycle. Yet, mammalian cells carrying Rb deletions are still able to arrest under growth-limiting conditions. The Rb-related proteins p107 and p130, which are components of the DREAM complex, had been suggested to be responsible for a continued ability to arrest by inhibiting E2f activity and by recruiting chromatin-modifying enzymes. Here, we show that p130 and p107 are not sufficient for DREAM-dependent repression. We identify the MuvB protein Lin37 as an essential factor for DREAM function. Cells not expressing Lin37 proliferate normally, but DREAM completely loses its ability to repress genes in G0/G1 while all remaining subunits, including p130/p107, still bind to target gene promoters. Furthermore, cells lacking both Rb and Lin37 are incapable of exiting the cell cycle. Thus, Lin37 is an essential component of DREAM that cooperates with Rb to induce quiescence.

中文翻译:

DREAM 复合体通过其亚基 Lin37 与 Rb 合作启动静止

视网膜母细胞瘤 Rb 蛋白是控制细胞周期的重要因素。然而,携带 Rb 缺失的哺乳动物细胞仍然能够在生长限制条件下停滞。Rb 相关蛋白 p107 和 p130 是 DREAM 复合物的组成部分,被认为是通过抑制 E2f 活性和招募染色质修饰酶来持续阻滞的原因。在这里,我们表明 p130 和 p107 不足以进行 DREAM 依赖性抑制。我们将 MuvB 蛋白 Lin37 确定为 DREAM 功能的重要因素。不表达 Lin37 的细胞正常增殖,但 DREAM 完全失去了抑制 G0/G1 基因的能力,而所有剩余的亚基,包括 p130/p107,仍与靶基因启动子结合。此外,缺乏 Rb 和 Lin37 的细胞无法退出细胞周期。
更新日期:2017-09-18
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