Journal article

Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity.

Yuchen Chien, Claudio Scuoppo, Xiaowo Wang, Xueping Fang, Brian Balgley, Jessica E Bolden, Prem Premsrirut, Weijun Luo, Agustin Chicas, Cheng S Lee, Scott C Kogan, Scott W Lowe

Genes Dev | Published : 2011

Abstract

Cellular senescence acts as a potent barrier to tumorigenesis and contributes to the anti-tumor activity of certain chemotherapeutic agents. Senescent cells undergo a stable cell cycle arrest controlled by RB and p53 and, in addition, display a senescence-associated secretory phenotype (SASP) involving the production of factors that reinforce the senescence arrest, alter the microenvironment, and trigger immune surveillance of the senescent cells. Through a proteomics analysis of senescent chromatin, we identified the nuclear factor-κB (NF-κB) subunit p65 as a major transcription factor that accumulates on chromatin of senescent cells. We found that NF-κB acts as a master regulator of the SA..

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University of Melbourne Researchers