Dataset Information

A20 contribution to NF-κB regulation, Ripoptosome formation and TNF-induced cell death [mouse]

ABSTRACT: A20 is known key regulator of NF-κB activity and inflammatory response, but its role in the control of cell death receptor signaling is not completely understood. Although A20 is widely accepted anti-apoptotic protein, we demonstrate that elevated expression of A20 in both, human and murine keratinocytes results in sensitisation to TNF-induced cell death. We prove that the Ripoptosome formation in A20 overexpressing cells is prerequisite for the TNF-induced cell death execution. We demonstrate that both canonical and non-canonical NF-κB signaling pathways are regulated upon increase of A20 expression. A20 dependent alteration of cIAPs and TRAF1 expressions are involved in the multiple level control of cell death in keratinocytes with elevated A20 expression. Overall design: The effects of A20 overexpression in tumor necrosis factor (TNF)-induced signalling were investigated in human and murine immortalized keratinocytes. This entry contains the results for the spontaneously immortalized murine keratinocytes.

INSTRUMENT(S): [MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version]

ORGANISM(S): Mus musculus

SUBMITTER: Guido Hooiveld

PROVIDER: GSE128248 | GEO | 2020-02-20

REPOSITORIES: GEO

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Publications

A20 Promotes Ripoptosome Formation and TNF-Induced Apoptosis via cIAPs Regulation and NIK Stabilization in Keratinocytes.

Feoktistova Maria M Makarov Roman R Brenji Sihem S Schneider Anne T AT Hooiveld Guido J GJ Luedde Tom T Leverkus Martin M Yazdi Amir S AS Panayotova-Dimitrova Diana D

Cells 20200203 2

The ubiquitin-editing protein A20 (TNFAIP3) is a known key player in the regulation of immune responses in many organs. Genome-wide associated studies (GWASs) have linked A20 with a number of inflammatory and autoimmune disorders, including psoriasis. Here, we identified a previously unrecognized role of A20 as a pro-apoptotic factor in TNF-induced cell death in keratinocytes. This function of A20 is mediated via the NF-κB-dependent alteration of cIAP1/2 expression. The changes in cIAP1/2 protei ...[more]

PMID: 32028675

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