Caspase-2 can trigger cytochrome C release and apoptosis from the nucleus

Gabriela Paroni, Clare Henderson, Claudio Schneider, Claudio Brancolini

Research output: Contribution to journalArticlepeer-review

Abstract

The cysteine proteases specific for aspartic residues, known as caspases, are localized in different subcellular compartments and play specific roles during the regulative and the executive phase of the cell death process. Here we investigated the subcellular localization of caspase-2 in healthy cells and during the execution of the apoptotic program. We have found that caspase-2 is a nuclear resident protein and that its import into the nucleus is regulated by two different nuclear localization signals. We have shown that in an early phase of apoptosis caspase-2 can trigger mitochondrial dysfunction from the nucleus without relocalizing into the cytoplasm. Release of cytochrome c occurs in the absence of overt alteration of the nuclear pores and changes of the nuclear/cytoplasmic barrier. Addition of leptomycin B, an inhibitor of nuclear export, did not interfere with the ability of caspase-2 to trigger cytochrome c release. Only during the late phase of the apoptotic process can caspase-2 relocalize in the cytoplasm, as consequence of an increase in the diffusion limits of the nuclear pores. Taken together these data indicate the existence of a nuclear/mitochondrial apoptotic pathway elicited by caspase-2.

Original languageEnglish
Pages (from-to)15147-61
Number of pages15
JournalJournal of Biological Chemistry
Volume277
Issue number17
DOIs
Publication statusPublished - Apr 26 2002

Keywords

  • Amino Acid Sequence
  • Apoptosis
  • Base Sequence
  • Caspase 2
  • Caspases/chemistry
  • Cell Line
  • Cell Nucleus/drug effects
  • Cytochrome c Group/metabolism
  • DNA Primers
  • Fatty Acids, Unsaturated/pharmacology
  • Humans
  • Molecular Sequence Data
  • Signal Transduction
  • Subcellular Fractions/enzymology

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