title: The tyrosine kinase c-Abl protects c-Jun from ubiquitination-mediated degradation in T cells.
abstract: 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.
authors.affiliation: Department of Otolaryngology--Head and Neck Surgery, University of Missouri-Columbia School of Medicine, Columbia, Missouri 65212, USA.
authors.forename: Beixue
authors.initials: B
authors.lastname: Gao
authors.forename: Sang-Myeong
authors.initials: SM
authors.lastname: Lee
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000378:metabolism; D025801:Ubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D025801:Ubiquitin; D019000:Phosphotyrosine; C471637:Itch protein, mouse; D044767:Ubiquitin-Protein Ligases; D016315:Proto-Oncogene Proteins c-abl