PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling.
Détails
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Etat: Public
Version: de l'auteur⸱e
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_80DD39813D98
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling.
Périodique
Molecular Cell
ISSN
1097-4164 (Electronic)
ISSN-L
1097-2765
Statut éditorial
Publié
Date de publication
2012
Volume
47
Numéro
5
Pages
681-693
Langue
anglais
Résumé
Biochemical evidence implicates the death-domain (DD) protein PIDD as a molecular switch capable of signaling cell survival or death in response to genotoxic stress. PIDD activity is determined by binding-partner selection at its DD: whereas recruitment of RIP1 triggers prosurvival NF-κB signaling, recruitment of RAIDD activates proapoptotic caspase-2 via PIDDosome formation. However, it remains unclear how interactor selection, and thus fate decision, is regulated at the PIDD platform. We show that the PIDDosome functions in the "Chk1-suppressed" apoptotic response to DNA damage, a conserved ATM/ATR-caspase-2 pathway antagonized by Chk1. In this pathway, ATM phosphorylates PIDD on Thr788 within the DD. This phosphorylation is necessary and sufficient for RAIDD binding and caspase-2 activation. Conversely, nonphosphorylatable PIDD fails to bind RAIDD or activate caspase-2, and engages prosurvival RIP1 instead. Thus, ATM phosphorylation of the PIDD DD enables a binary switch through which cells elect to survive or die upon DNA injury.
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/12/2012 11:40
Dernière modification de la notice
20/08/2019 15:41