Mel-18, a polycomb group protein, regulates cell proliferation and senescence via transcriptional repression of Bmi-1 and c-Myc oncoproteins

被引:124
作者
Guo, Wei-Jian
Datta, Sonal
Band, Vimla
Dimri, Goberdhan P. [1 ]
机构
[1] Evanston NW Healthcare Res Inst, Div Canc Biol, Evanston, IL 60201 USA
[2] Evanston NW Healthcare Res Inst, Dept Med, Evanston, IL 60201 USA
[3] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Evanston, IL 60201 USA
[4] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60201 USA
关键词
D O I
10.1091/mbc.E06-05-0447
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页码:536 / 546
页数:11
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