| The nonreceptor tyrosine kinase c-Abl is ubiquitously expressed and highly conserved in evolution. Its sub-cellular localization plays crucial role in determining the outcome of c-Abl activation in response to different stimuli. Indeed, c-Abl is activated in the cytoplasm upon many stimulations and its activity has been implicated in cell division, cell differentiation, cell adhesion and stress response. Conversely, in the nucleus, c-Abl is activated during the apoptotic response to DNA damage and regulates the cell cycle arrest in G1 phase. c-Abl can shuttle between the cytoplasm and the nucleus mediated by three NLSs (nuclear localization signal) and one NES (nuclear export signal) in its C-terminal domain. In sharp contrast, all transforming Abl variants are exclusively cytoplasmic, such as Bcr-Abl, even though which contains same NLS and NES sequence as c-Abl. It is critical in inducing human chronic myelogenous leckemia (CML). The mechanisms of nucleo-cytoplasmic transportation of c-Abl are not well known at present.To identify potential targets that are responsible for regulating the sublocalization of c-Abl kinase, the yeast two-hybrid system is utilized to screen a Hela cDNA library, using the wild c-Abl Ib as bait. One c-Abl binding protein of particular interest was nucleoporin p62 of nuclear pore complex (NPC), which is embedding in the nuclear envelope and as the unique channel for trafficking macromolecules between the nuclear and cytoplasmic compartments. p62 is localized in the central channel of NPC and play an important role in nuclear transport. In this study, the interaction between c-Abl and p62 was identified by yeast two hybridization, co-immunoprecipiation and in vitro binding assay. Direct association of c-Abl with p62 P299 site was demonstrated, and the SH3 domain of c-Abl was required. p62 was partially phosphorylated by c-Abl. c-Abl could bind more monomer and dimer of p62 in response to DNA damage induced by...
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