Abstract
The c-Abl tyrosine kinase and its transforming variants have been implicated in tumorigenesis and in many important cellular processes. c-Abl is localized in the nucleus and the cytoplasm, where it plays distinct roles. The effects of c-Abl are mediated by multiple protein-protein and protein-DNA interactions and its tyrosine kinase domain. At the biochemical level, the mechanism of c-Abl kinase activation and the identification of its target proteins and cellular machineries have in part been solved. However, the phenotypic outcomes of these molecular events remained in large elusive. c-Abl has been shown to regulate the cell cycle and to induce under certain conditions cell growth arrest and apoptosis. In this respect the interaction of c-Abl with p53 and p73 has attracted particular attention. Recent findings have implicated c-Abl in an ionizing irradiation signaling pathway that elicits apoptosis. In this pathway p73 is an important immediate downstream effector. Here I review the current knowledge about these nuclear processes in which c-Abl is engaged and discuss some of their possible implications on cell physiology.
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Abbreviations
- ATM:
-
ataxia-telangiectasia mutant
- CTD:
-
C-terminus domain
- EIAV:
-
equine infectious anaemia virus
- HBV:
-
hepatitis B virus
- IR:
-
ionizing irradiation
- NES:
-
nuclear export signal
- NLS:
-
nuclear localization signal
- SH:
-
Src homology
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I would like to thank Y Katan-Khaykovich for critical reading and helpful comments.
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Shaul, Y. c-Abl: activation and nuclear targets. Cell Death Differ 7, 10–16 (2000). https://doi.org/10.1038/sj.cdd.4400626
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DOI: https://doi.org/10.1038/sj.cdd.4400626
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