Polycomb group (PcG) protein Bmi-1 is an important regulator of cell proliferation. It regulates cellular senescence and proliferation of cells via the transcriptional repression of INK4a/ARF locus and other target genes. Here, we report that Mel-18, a PcG ring finger protein (PCGF) transcriptionally down-regulates Bmi-1. Furthermore, the expression of Bmi-1 and Mel-18 inversely correlates in proliferating and senescent human fibroblasts. Bmi-1 down-regulation by Mel-18 results in accelerated senescence and shortening of the replicative life span in normal human cells. Importantly, using promoter-reporter, chromatin immunoprecipitation, and quantitative real-time primary transcript RT-PCR assays, and an RNA interference approach, we demonstrate that Bmi-1 is a bona fide target of c-Myc oncoprotein. Finally, our data suggest that Mel-18 regulates Bmi-1 expression during senescence via down-regulation of c-Myc. These studies link c-Myc and polycomb function in cell proliferation and senescence.

译文

:Polycomb group(PcG)蛋白Bmi-1是细胞增殖的重要调节剂。它通过INK4a / ARF基因座和其他靶基因的转录抑制来调节细胞的衰老和细胞增殖。在这里,我们报道Mel-18,一种PcG无名指蛋白(PCGF)转录下调Bmi-1。此外,在增殖和衰老的人类成纤维细胞中,Bmi-1和Mel-18的表达呈负相关。 Mel-18对Bmi-1的下调会导致正常人细胞中加速衰老并缩短复制寿命。重要的是,使用启动子-报告子,染色质免疫沉淀和定量实时初级转录RT-PCR分析以及RNA干扰方法,我们证明Bmi-1是c-Myc癌蛋白的真正靶标。最后,我们的数据表明,Mel-18通过下调c-Myc调节衰老过程中Bmi-1的表达。这些研究将c-Myc和多梳功能与细胞增殖和衰老联系起来。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录