The tyrosine kinase c-Abl protects c-Jun from ubiquitination-mediated degradation in T cells.

The cross-talk of ubiquitination with other types of posttranscriptional modifications, such as phosphorylation, regulates the stability of many proteins. We have previously demonstrated that c-Jun is a substrate of Itch, a HECT-type E3 ubiquitin ligase. c-Jun is also a substrate of the tyrosine kinase c-Abl. Here we report that genetic ablation of c-Abl accelerated c-Jun degradation. Phosphorylation of the tyrosine within the PPXY motif by c-Abl inhibited c-Jun ubiquitination and its binding by Itch. The nuclear localization of c-Abl, triggered by T-cell activation signals, was essential for its activity in regulating c-Jun transcription activity. These findings define a potential molecular mechanism for the immunodeficiency in mice lacking the c-abl gene.