c-Abl: activation and nuclear targets

The c-Abl tyrosine kinase and its transforming variants have been implicate d in tumorigenesis and in many important cellular processes. c-Abl is local ized in the nucleus and the cytoplasm, where it plays distinct roles. The e ffects of c-Abl are mediated by multiple protein-protein and protein-DNA in teractions and its tyrosine kinase domain. At the biochemical level, the me chanism of c-Abl kinase activation and the identification of its target pro teins and cellular machineries have in part been solved. However, the pheno typic outcomes of these molecular events remained in large elusive. c-Abl h as been shown to regulate the cell cycle and to induce under certain condit ions cell growth arrest and apoptosis. In this respect the interaction of c -Abl with p53 and p73 has attracted particular attention. Recent findings h ave implicated c-Abl in an ionizing irradiation signaling pathway that elic its apoptosis. In this pathway p73 is an important immediate downstream eff ector. 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.