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Suppression of p53-mediated senescence by non-canonical NF-kappaB pathway mediated regulation of EZH2 expression

ABSTRACT: The NF-kappaB and p53 transcription factors control the expression of complex gene regulatory networks in response to many cell stresses and stimuli. This experiment describes gene expression profiling of cells depleted for EZH2, NF-kappaB2, RelB and p53. We find that EZH2 is the major effector of crosstalk between the alternative NF-kappaB and p53 pathways and acts to suppress cellular senescence. Total RNA was obtained from primary juvenile human dermal fibroblasts 48 hours after transfection with siRNA specific for one, or a targeted combination of the transcription factors, or a scrambled siRNA control.

ORGANISM(S): Homo sapiens

SUBMITTER: Simon Cockell

PROVIDER: E-MTAB-1593 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Regulation of p53 and Rb links the alternative NF-κB pathway to EZH2 expression and cell senescence.

Iannetti Alessio A Ledoux Adeline C AC Tudhope Susan J SJ Sellier Hélène H Zhao Bo B Mowla Sophia S Moore Adam A Hummerich Holger H Gewurz Benjamin E BE Cockell Simon J SJ Jat Parmjit S PS Willmore Elaine E Perkins Neil D ND

PLoS genetics 20140925 9

There are two major pathways leading to induction of NF-κB subunits. The classical (or canonical) pathway typically leads to the induction of RelA or c-Rel containing complexes, and involves the degradation of IκBα in a manner dependent on IκB kinase (IKK) β and the IKK regulatory subunit NEMO. The alternative (or non-canonical) pathway, involves the inducible processing of p100 to p52, leading to the induction of NF-κB2(p52)/RelB containing complexes, and is dependent on IKKα and NF-κB inducing ...[more]

PMID: 25255445

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