Interaction Of C-Abl And Ubiquitin-like Protein HPLIC-2

Human PLIC-2(hPLIC-2), the homologues of yeast Dsk2 and mouse PLICs(proteins link IAP and cytoskeleton,PLICs), is implicated in the degradation of proteins by ubiquitin-proteasome pathway. It may function as a carrier of ubiquitinated substrates and provide a link between proteasome and ubiquitin machinery. In this study, it was demonstrated that the ubiquitously expressed non-receptor tyrosine kinases, c-Abl and Arg, bind directly with the UBA domain of hPLIC-2 via its N terminal region which contains SH3, SH2 and kinase domain. It was also revealed that hPLIC-2 was not phosphorylated by c-Abl. Overexpression of c-Abl resulted in increased amount of ubiquitinated proteins in the cells. Significantly, It was shown that reactive oxygen species (ROS) enhanced the association of hPLIC-2 with c-Abl. The Amount of hPLIC-2 binding ubiquitinated proteins was increased in the presence of c-Abl, and the association of hPLIC-2 with proteasome was also shown potentiated by c-Abl. In summary, c-Abl may involved in protein degradation in ubiquitin-proteasome pathway by enhancing substrate recruition and association of ubiquitinated protein with proteasomes. It highlights a new mechanism by which c-Abl regulates protein degradation.