期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 31, 期 13, 页码 2707-2714出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.05133-11
关键词
-
资金
- NIH [AG30323, HD37267]
- [HD07312]
CPEB is a sequence-specific translational regulatory RNA binding protein that mediates cellular senescence in primary mouse and human cells. CPEB knockout mouse embryo fibroblasts (MEFs) bypass senescence and synthesize large amounts of interleukin-6 (IL-6) and many other cytokines, which is not the case with either wild-type MEFs immortalized by prolonged culture or p53-deficient MEFs. CPEB regulates the production of IL-6 at both the translational and transcriptional levels; in CPEB-depleted cells, aberrant IL-6 transcription is mediated by improper NF-kappa B p65 phosphorylation and nuclear localization. Although IL-6 strengthens the senescence of wild-type cells, it has no effect on CPEB-deficient cells, even though they produce prodigious amounts of the cytokine. IL-6-promoted entry into senescence requires p53; CPEB knockout MEFs, however, synthesize only similar to 50% of the p53 of wild-type MEFs, which is insufficient to respond to IL-6. Thus, CPEB deficiency not only increases IL-6 production but also renders the cell incapable of a senescence-promoting response.
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