The enigma of caspase-2: the laymen's view

doi:doi:10.1038/cdd.2008.170

Abstract

Proteolysis of cellular substrates by caspases (cysteine-dependent aspartate-specific proteases) is one of the hallmarks of apoptotic cell death. Although the activation of apoptotic caspases is considered a 'late-stage' event in apoptosis signaling, past the commitment stage, one caspase family member, caspase-2, splits the cell death community into half – those searching for evidence of an apical initiator function of this molecule and those considering it as an amplifier of the apoptotic caspase cascade, at best, if relevant for apoptosis at all. This review screens past and present biochemical as well as genetic evidence for caspase-2 function in cell death signaling and beyond.

Keywords:

caspase-2, caspase activity, caspase activation platform, DNA damage, ER stress, PIDD, RAIDD

Abbreviations:

ARC, apoptosis repressor with a CARD; ATM, Ataxia telangiectasia mutated; ATR, Ataxia telangiectasia and Rad3 related; b-VAD-fmk, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone; CaMKII, calcium/calmodulin-dependent protein kinase II; CARD, caspase activation and recruitment domain; Chk1, check-point kinase 1; clAP1, cellular inhibitor of apoptosis protein; CRADD, Caspase-2 and RIPK1 domain containing adaptor with death domain; DED, death effector domain; DEFCAP, death effect or filament-forming Ced-4-like apoptosis protein; DFF-45/ICAD, DNA fragmentation factor 45/inhibitor of caspase-dependent DNase; DISC, death-inducing signalling complex; DR, death receptor; FADD, Fas-associated death domain; GMEB1, glucocorticoid modulatory element-binding protein 1; Htt, Huntigtin; Ich-1, ICE/CED-3 homologue 1; MEF, mouse embryonic fibroblast; MOMP, mitochondrial outer membrane permeabilization; Nedd-2, neural precursor cells-expressed, developmentally down-regulated; NLS, nuclear localization signal; PACAP, pro-apoptotic caspase adaptor protein; PIDD, p53-induced protein with a death domain; PKCK2, protein kinase casein kinase 2; PML-NBs, promyelocytic leukemia nuclear bodies; RAIDD, RIP-associated ICH-1/CED-3 homologous protein with a death domain; RIP, receptor-interacting protein; SUMO, small ubiquitin-like modifier; TRADD, TNF-R1-associated death domain protein; TNF-R1, tumour necrosis factor receptor 1; TRAIL, tumor necrosis factor related apoptosis inducing ligand; Ubc9, SUMO-conjugating enzyme 9

Review