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Friend or foe: emerging role of nuclear factor kappa-light-chain-enhancer of activated B cells in cell senescence

Authors Mowla SN, Perkins ND, Jat PS

Published Date September 2013 Volume 2013:6 Pages 1221—1229


Received 6 June 2013, Accepted 10 July 2013, Published 4 September 2013

Sophia N Mowla,1 Neil D Perkins,2 Parmjit S Jat1

1Department of Neurodegenerative Disease and MRC Prion Unit, UCL Institute of Neurology, Queen Square, London, UK; 2Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

Abstract: The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) proteins are a family of ubiquitously expressed transcription factors that regulate the response to cellular stress. They mediate innate and adaptive immunity through the initiation of an inflammatory response to pro-inflammatory signals. The role of persistent inflammation in aiding tumor development has led to the NF-κB family of transcription factors being strongly implicated in promoting cancer. However, recent studies have now revealed that NF-κB can also function as a tumor suppressor through the induction of cellular senescence. Cellular senescence is a stable cell cycle arrest that normal cells undergo in response to a variety of intrinsic and extrinsic stimuli including: progressive telomere shortening, changes in telomeric structure, or other forms of genotoxic stress. Senescence can compromise tissue repair and regeneration, contributing to tissue and organismal aging via the accumulation of senescent cells, depletion of stem/progenitor cells and secretion of an array of inflammatory cytokines, chemokines, and matrix metalloproteinases. Senescence can also lead to the removal of potentially cancerous cells, thereby acting as a potent tumor suppressor mechanism. Herein, we review the evidence indicating a role for NF-κB in tumor suppression via cellular senescence and suggest that depending upon the subunit expressed, the biological context, and the type and intensity of the signal, NF-κB can indeed promote senescence growth arrest.

Keywords: cell senescence, growth arrest, NF-κB, SASP

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