Perturbation of ribosome biogenesis drives cells into senescence through 5S RNP-mediated p53 activation - PubMed (original) (raw)

. 2015 Mar 3;10(8):1310-23.

doi: 10.1016/j.celrep.2015.01.055. Epub 2015 Feb 26.

Affiliations

Free article

Perturbation of ribosome biogenesis drives cells into senescence through 5S RNP-mediated p53 activation

Kazuho Nishimura et al. Cell Rep. 2015.

Free article

Abstract

The 5S ribonucleoprotein particle (RNP) complex, consisting of RPL11, RPL5, and 5S rRNA, is implicated in p53 regulation under ribotoxic stress. Here, we show that the 5S RNP contributes to p53 activation and promotes cellular senescence in response to oncogenic or replicative stress. Oncogenic stress accelerates rRNA transcription and replicative stress delays rRNA processing, resulting in RPL11 and RPL5 accumulation in the ribosome-free fraction, where they bind MDM2. Experimental upregulation of rRNA transcription or downregulation of rRNA processing, mimicking the nucleolus under oncogenic or replicative stress, respectively, also induces RPL11-mediated p53 activation and cellular senescence. We demonstrate that exogenous expression of certain rRNA-processing factors rescues the processing defect, attenuates p53 accumulation, and increases replicative lifespan. To summarize, the nucleolar-5S RNP-p53 pathway functions as a senescence inducer in response to oncogenic and replicative stresses.

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources