PIDD Death-Domain Phosphorylation by ATM Controls Prodeath versus Prosurvival PIDDosome Signaling
| Autor: | Emmanuelle Logette, A. Thomas Look, Jianlong Wang, Kiyohiro Ando, Jürg Tschopp, Takaomi Sanda, Jennifer L. Kernan, Lisa Bouchier-Hayes, Samuel Sidi, Peter H. Liu |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Death Domain Receptor Signaling Adaptor Proteins
Cell Survival DNA damage Caspase 2 CRADD Signaling Adaptor Protein Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases DNA-binding protein Humans Phosphorylation Molecular Biology Cells Cultured Death domain Cell Death biology Tumor Suppressor Proteins Cell Biology Cell biology DNA-Binding Proteins HEK293 Cells Cancer research biology.protein Signal transduction DNA Damage HeLa Cells Signal Transduction |
| Zdroj: | Molecular Cell, vol. 47, no. 5, pp. 681-693 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2012.06.024 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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