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Mol Cell Biol. 2011 Jul;31(13):2707-14. doi: 10.1128/MCB.05133-11. Epub 2011 May 2.

CPEB control of NF-kappaB nuclear localization and interleukin-6 production mediates cellular senescence.

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  • 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Abstract

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-κB 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 ∼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.

PMID:
21536657
[PubMed - indexed for MEDLINE]
PMCID:
PMC3133380
Free PMC Article

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