The unpredictable caspase-2: what can it do?
Caspase-2, the most conserved member of the caspase family, has long been recognized as an important protein in the regulation of apoptosis. However, due to a lack of phenotype in caspase-2 knock-out mice, its precise role has been questioned. Recently, several publications have described new mechanisms regulating caspase-2 activation, including its role within an activating complex named the PIDDosome, linking caspase-2 function to p53. Consistent with this, evidence is accumulating for potential roles of caspase-2 in non-apoptotic processes, including cell cycle regulation and DNA repair. In addition, a tumor-suppressor function has been suggested for caspase-2. Here we discuss how different PIDDosome complexes could be involved in mechanisms regulating the switch between the various functions of caspase-2.
Vakifahmetoglu-Norberg
Helin
H
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Zhivotovsky
Boris
B
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053420:CRADD Signaling Adaptor Protein / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D053143:Caspase 2 / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology; D053418:Death Domain Receptor Signaling Adaptor Proteins; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology
D053420:CRADD Signaling Adaptor Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; C485896:PIDD1 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D053143:Caspase 2