The role of caspase-2 in stress-induced apoptosis

Abstract

Caspase-2 is the most evolutionarily conserved of all the caspases, yet it has a poorly defined role in apoptotic pathways. This is mainly due to a dearth of techniques to determine the activation status of caspase-2 and the lack of an abnormal phenotype in caspase-2 deficient mice. Nevertheless, emerging evidence suggests that caspase-2 may have important functions in a number of stress-induced cell death pathways, in cell cycle maintenance and regulation of tumour progression. This review discusses recent advances that have been made to help elucidate the true role of this elusive caspase and the potential contribution of caspase-2 to the pathology of human diseases including cancer.

Fig 1

Schematic of the caspase-2 protein. The proposed mechanism of caspase-2 processing that occurs upon dimerization is shown. Note only one member of the dimer is depicted. C320 represents the active site cysteine.

Fig 2

The caspase-2 activation pathway. A schematic representation of the proposed mechanism for capase-2 activation by the PIDDosome. Inactive caspase-2 monomers are recruited to the PIDDosome in response to certain cellular stresses. This results in dimerization and activation of caspase-2. Caspase-2 cleaves and activates Bid to induce MOMP eventually resulting in activation of executioner caspases by caspase-9-mediated cleavage.