Abstract
P53-induced protein with a death domain (PIDD) was cloned as a death domain (DD)-containing protein whose expression is induced by p53. It was later described as the core of a molecular platform-activating caspase-2, named the PIDDosome. These first results pointed towards a role for PIDD in apoptosis, in response to DNA damage. Identification of new PIDDosome complexes involved in DNA repair and nuclear factor-κB signaling challenged this early concept. PIDD functions are growing as new complexes and new interaction partners are being discovered, and as additional functions are being revealed. A fascinating feature of PIDD lies within its complex and tight regulation mechanisms, which allow the molecule to fine-tune its different functions: from transcriptional regulation to the expression of different isoforms, and from the interaction with regulatory proteins to an ingenious post-translational cleavage mechanism generating various active fragments with specific functions. Further studies still need to be carried out to provide answers to many unresolved issues and to reconcile conflicting results. This review aims at providing an overview of the current PIDD knowledge status.
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Abbreviations
- Apaf-1:
-
apoptotic protease-activating factor 1
- CARD:
-
caspase activation and recruitment domain
- Chk1:
-
checkpoint kinase 1
- DD:
-
death domain
- ER:
-
endoplasmic reticulum
- IAP:
-
inhibitor of apoptosis protein
- kDa:
-
kiloDalton
- LRDD:
-
leucine-rich repeats containing protein with a death domain
- LRR:
-
leucine-rich repeats
- ∣NF-κB:
-
nuclear factor-κB
- NLR:
-
Nod-like receptors
- NLRP3:
-
Nod-like receptors protein 3
- PCNA:
-
proliferating cell nuclear antigen
- PIDD:
-
p53-induced protein with a death domain
- RAIDD:
-
RIP-associated ICH-1/CED-3 homologous protein with a death domain
- RIP:
-
receptor-interacting protein
- siRNA:
-
small interfering RNA
- UPA:
-
uncharacterized protein domain in UNC5, PIDD and Ankyrin family of proteins
- VAD-fmk:
-
N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
- ZUD:
-
Zu5 and DD-containing inhibitor of NF-κB
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Acknowledgements
We thank all members of the group Tschopp who over the years helped in unraveling the functions of this fascinating protein PIDD: S Lippens, S Cuenin, E Logette, M Eckert, and K Ludigs. We would further like to thank N Aebi, S Hertig, and C Mattmann for their excellent technical support and all group Tschopp members for the fantastic discussions over the years.
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Janssens, S., Tinel, A. The PIDDosome, DNA-damage-induced apoptosis and beyond. Cell Death Differ 19, 13–20 (2012). https://doi.org/10.1038/cdd.2011.162
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DOI: https://doi.org/10.1038/cdd.2011.162
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