title: Caspase-2 promotes cytoskeleton protein degradation during apoptotic cell death.
abstract: The caspase family of proteases cleaves large number of proteins resulting in major morphological and biochemical changes during apoptosis. Yet, only a few of these proteins have been reported to selectively cleaved by caspase-2. Numerous observations link caspase-2 to the disruption of the cytoskeleton, although it remains elusive whether any of the cytoskeleton proteins serve as bona fide substrates for caspase-2. Here, we undertook an unbiased proteomic approach to address this question. By differential proteome analysis using two-dimensional gel electrophoresis, we identified four cytoskeleton proteins that were degraded upon treatment with active recombinant caspase-2 in vitro. These proteins were degraded in a caspase-2-dependent manner during apoptosis induced by DNA damage, cytoskeleton disruption or endoplasmic reticulum stress. Hence, degradation of these cytoskeleton proteins was blunted by siRNA targeting of caspase-2 and when caspase-2 activity was pharmacologically inhibited. However, none of these proteins was cleaved directly by caspase-2. Instead, we provide evidence that in cells exposed to apoptotic stimuli, caspase-2 probed these proteins for proteasomal degradation. Taken together, our results depict a new role for caspase-2 in the regulation of the level of cytoskeleton proteins during apoptosis.
authors: Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 171 77, Sweden.
authors: H
authors: H
authors: Vakifahmetoglu-Norberg
authors: E
authors: E
authors: Norberg
authors: A B
authors: AB
authors: Perdomo
authors: M
authors: 0000000263708423
authors: M
authors: Olsson
authors: F
authors: F
authors: Ciccosanti
authors: S
authors: S
authors: Orrenius
authors: G M
authors: GM
authors: Fimia
authors: M
authors: M
authors: Piacentini
authors: B
authors: B
authors: Zhivotovsky
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D053143:Caspase 2 / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D059865:Endoplasmic Reticulum Stress; D045325:HCT116 Cells; D006801:Humans; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D003598:Cytoskeletal Proteins; C490360:CASP2 protein, human; D053143:Caspase 2; D003546:Cysteine Endopeptidases