Open AccessCaspase-Dependent Cleavage of c-Abl Contributes to Apoptosis
Author(s) -
Daniela Barilá,
Alessandra Rufini,
Ivano Condò,
Natascia Ventura,
Karel Dorey,
Giulio SupertiFurga,
Roberto Testi
Publication year - 2003
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.23.8.2790-2799.2003
Subject(s) - biology , microbiology and biotechnology , caspase , death domain , cleavage (geology) , apoptosis , tyrosine kinase , abl , cell nucleus , nuclear localization sequence , nuclear export signal , fas receptor , caspase 8 , programmed cell death , signal transduction , cytoplasm , biochemistry , paleontology , fracture (geology)
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.