Caspase-2 promotes cytoskeleton protein degradation during apoptotic cell death

H. Vakifahmetoglu-Norberg, E. Norberg, A. B. Perdomo, M. Olsson, F. Ciccosanti, S. Orrenius, G. M. Fimia, M. Piacentini, B. Zhivotovsky

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere940
JournalCell Death and Disease
Volume4
Issue number12
DOIs
Publication statusPublished - Dec 2013

Keywords

  • apoptosis
  • caspase-2
  • cytoskeleton protein
  • protein degradation
  • proteomics

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

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  • Cite this

    Vakifahmetoglu-Norberg, H., Norberg, E., Perdomo, A. B., Olsson, M., Ciccosanti, F., Orrenius, S., Fimia, G. M., Piacentini, M., & Zhivotovsky, B. (2013). Caspase-2 promotes cytoskeleton protein degradation during apoptotic cell death. Cell Death and Disease, 4(12), [e940]. https://doi.org/10.1038/cddis.2013.463