Abstract
Despite an abundance of literature on the role of caspase-2 in apoptosis, there exists much controversy about this protease making it difficult to place caspase-2 correctly in the apoptotic cascade, and hence its role in apoptosis remains unclear. The identification of the PIDDosome as a signaling platform for caspase-2 activation prompted intense investigation into the true role of this orphan caspase. What has emerged is the idea that caspase-2 may not be mandatory for apoptosis and that activation of this caspase in response to some forms of stress has other effects on the cell such as regulation of cell cycle progression. This idea is particularly relevent to the discovery that caspase-2 may act as a tumor suppressor. Here, we discuss the proposed mechanisms through which caspase-2 signals, in particular those involving PIDD, and their impact on cellular fate.
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Abbreviations
- ALL:
-
acute lymphoblastic leukemia
- APAF-1:
-
apoptotic protease-activating factor-1
- ATM:
-
ataxia telangiectasia mutated
- CARD:
-
caspase recruitment domain
- Chk1:
-
checkpoint kinase 1
- DD:
-
death domain
- IκB:
-
inhibitor of κB
- LRR:
-
leucine-rich repeat
- Mdm2:
-
mammalian double minute 2
- NALP, NACHT:
-
LRR and PYD domains-containing protein
- NEMO:
-
NFκB essential modulator
- NFκB:
-
nuclear factor κB
- NOD:
-
nucleotide-binding oligomerization domain
- PCNA:
-
proliferating cell nuclear antigen
- PIDD:
-
p53-induced protein with a death domain
- PP1:
-
protein phosphatase 1
- RAIDD:
-
RIP-associated ICH-1/CAD-3 homologous protein with a death domain
- RIPK1:
-
receptor interacting protein kinase 1
- SUMO:
-
small ubiquitin-like modifier
- TNF:
-
tumor necrosis factor
- TNFR1:
-
tumor necrosis factor receptor 1
- TRADD:
-
tumor necrosis factor receptor type 1-associated death domain protein
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Acknowledgements
It is with immeasurable sadness that we offer this small testimony to the life and a few of the myriad contributions of our friend, Professor Jürg Tschopp. Jürg was a valued colleague, great friend and a brilliant scientist. One other small contribution is noted in another field, that of skiing; Dr Tschopp was the first to force one of us (DRG) to navigate the treacherous double-black diamond run, called ‘The Devil′s Crotch’ on Breckenridge Mountain (Jürg skied it effortlessly, while DRG did it significantly less so, but the latter has skied it since with fond memories). We will miss you in so many ways, Jürg.
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Bouchier-Hayes, L., Green, D. Caspase-2: the orphan caspase. Cell Death Differ 19, 51–57 (2012). https://doi.org/10.1038/cdd.2011.157
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DOI: https://doi.org/10.1038/cdd.2011.157
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