c-Abl: activation and nuclear targets.
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. Cell Death and Differentiation (2000) 7, 10 - 16.
Shaul
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Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. yosef.shaul@weizmann.ac.il
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D004789:Enzyme Activation; D016193:G1 Phase; D006801:Humans; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013347:Subcellular Fractions; D014158:Transcription, Genetic
D004247:DNA; D016315:Proto-Oncogene Proteins c-abl