Caspase-dependent cleavage of c-Abl contributes to apoptosis

Daniela Barilà, Alessandra Rufini, Ivano Condò, Natascia Ventura, Karel Dorey, Giulio Superti-Furga, Roberto Testi

Research output: Contribution to journalArticlepeer-review


The nonreceptor tyrosine kinase c-Abl may contribute to the regulation of apoptosis. c-Abl activity is induced in the nucleus upon DNA damage, and its activation is required for execution of the apoptotic program. Recently, activation of nuclear c-Abl during death receptor-induced apoptosis has been reported; however, the mechanism remains largely obscure. Here we show that c-Abl is cleaved by caspases during tumor necrosis factor- and Fas receptor-induced apoptosis. Cleavage at the very C-terminal region of c-Abl occurs mainly in the cytoplasmic compartment and generates a 120-kDa fragment that lacks the nuclear export signal and the actin-binding region but retains the intact kinase domain, the three nuclear localization signals, and the DNA-binding domain. Upon caspase cleavage, the 120-kDa fragment accumulates in the nucleus. Transient-transfection experiments show that cleavage of c-Abl may affect the efficiency of Fas-induced cell death. These data reveal a novel mechanism by which caspases can recruit c-Abl to the nuclear compartment and to the mammalian apoptotic program.

Original languageEnglish
Pages (from-to)2790-2799
Number of pages10
JournalMolecular and Cellular Biology
Issue number8
Publication statusPublished - Apr 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology


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