PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling.

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Serval ID
serval:BIB_80DD39813D98
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling.
Journal
Molecular Cell
Author(s)
Ando K., Kernan J.L., Liu P.H., Sanda T., Logette E., Tschopp J., Look A.T., Wang J., Bouchier-Hayes L., Sidi S.
ISSN
1097-4164 (Electronic)
ISSN-L
1097-2765
Publication state
Published
Issued date
2012
Volume
47
Number
5
Pages
681-693
Language
english
Abstract
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
Yes
Create date
07/12/2012 11:40
Last modification date
20/08/2019 15:41
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