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Article Dans Une Revue Cell Death and Disease Année : 2020

The E3 ligase UBR2 regulates cell death under caspase deficiency via Erk/MAPK pathway

Elodie Villa
  • Fonction : Auteur
Rachel Paul
Ophélie Meynet
  • Fonction : Auteur
Sophie Volturo
  • Fonction : Auteur
Jean-Ehrland Ricci
  • Fonction : Auteur

Résumé

Escape from cell death is a key event in cancer establishment/progression. While apoptosis is often considered as the main cell death pathway, upon caspase inhibition, cell death is rather delayed than blocked leading to caspase-independent cell death (CICD). Although described for years, CICD's underlying mechanism remains to be identified. Here, we performed a genome-wide siRNA lethality screening and identified the RING-Type E3 Ubiquitin Transferase (UBR2) as a specific regulator of CICD. Strikingly, UBR2 downregulation sensitized cells towards CICD while its overexpression was protective. We established that UBR2-dependent protection from CICD was mediated by the MAPK/Erk pathway. We then observed that UBR2 is overexpressed in several cancers, especially in breast cancers and contributes to CICD resistance. Therefore, our work defines UBR2 as a novel regulator of CICD, found overexpressed in cancer cells, suggesting that its targeting may represent an innovative way to kill tumor cells.

Dates et versions

hal-03102334 , version 1 (07-01-2021)

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Citer

Elodie Villa, Rachel Paul, Ophélie Meynet, Sophie Volturo, Guillaume Pinna, et al.. The E3 ligase UBR2 regulates cell death under caspase deficiency via Erk/MAPK pathway. Cell Death and Disease, 2020, 11 (12), pp.1041. ⟨10.1038/s41419-020-03258-3⟩. ⟨hal-03102334⟩
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