Abstract
Cellular senescence is a program of irreversible cell cycle arrest that cells undergo in response to a variety of intrinsic and extrinsic stimuli including progressive shortening of telomeres, changes in telomeric structure or other forms of genotoxic and non-genotoxic stress. The role of nuclear factor-κB in cellular senescence is controversial, as it has been associated with both proliferation and tumour progression, and also with growth arrest and ageing. This research perspective focuses on the evidence for a functional relationship between NF-κB and senescence, and how disruption of the NF-κB pathway can lead to its bypass.
Highlights
Cellular senescence is a program of irreversible cell cycle arrest that cells undergo in response to a variety of intrinsic and extrinsic stimuli including progressive shortening of telomeres, changes in telomeric structure or other forms of genotoxic and non‐genotoxic stress
Blagosklonny has proposed that senescence involves two steps: cell cycle arrest and an activation of intracellular signalling pathways which result in cellular hypertrophy and a pro-inflammatory and hyper-secretory phenotype [7,8,9]
The role of nuclear factor (NF)- κB in senescence is controversial, as it is divisively associated with proliferation and tumour progression, and contrastingly with growth arrest and ageing
Summary
Cellular senescence is a program of irreversible cell cycle arrest that cells undergo in response to a variety of intrinsic and extrinsic stimuli including progressive shortening of telomeres, changes in telomeric structure or other forms of genotoxic and non‐genotoxic stress. This leads to activation of the pRB tumour suppressor pathway in which the hypophosphorylated pRB family of proteins complex with E2F heterodimers, thereby preventing cell cycle progression [2,3,4]. The pRB pathway can be activated independently of p53 by upregulation of p16INK4A upon non-genotoxic stress, which inhibits cyclinD-CDK4/6 complexes from phosphorylating the pRB family of proteins [2,3,4].
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