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2012
- doi: 10.1016/j.molcel.2012.06.024
- issn: 1097-2765
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Sujets proches
Damage, DNA Survival skills Survival after airplane accidents, shipwrecks, etc Analysis (Mathematics) Proof Deoxyribonucleic acid TNA (Nucleic acid) Desoxyribonucleic acid Thymonucleic acid Death--Philosophy Dying End of lifeCiter ce document
K. Ando et al., « PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling. », Serveur académique Lausannois, ID : 10.1016/j.molcel.2012.06.024
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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.