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Cell Death & Differentiation
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c-Abl: activation and nuclear targets

Cell Death & Differentiationvolume 7, pages10–16 (2000)Cite this article

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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Acknowledgements

I would like to thank Y Katan-Khaykovich for critical reading and helpful comments.

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Authors and Affiliations

  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel

    Y Shaul

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  1. Y Shaul

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Correspondence toY Shaul.

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