Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl.
The mechanisms leading to the ubiquitination and degradation of the activated c-Abl kinase have not yet been identified. We found that the multi-adaptor protein ArgBP2 links c-Abl to the ubiquitin ligase Cbl. Phosphorylation of Cbl and ArgBP2 by c-Abl resulted in the stabilization of their interactions, thus facilitating Cbl-induced ubiquitination and subsequent degradation of c-Abl and ArgBP2.
Soubeyran
Philippe
P
Ludwig Institute for Cancer Research, Box 595, Husargatan 3, Uppsala, S-75124, Sweden.
Barac
Ana
A
Szymkiewicz
Iwona
I
Dikic
Ivan
I
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D050722:Oncogene Protein v-cbl; D010766:Phosphorylation; D011485:Protein Binding; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D016601:RNA-Binding Proteins; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D050722:Oncogene Protein v-cbl; D016601:RNA-Binding Proteins; D015682:Retroviridae Proteins, Oncogenic; C490755:SORBS2 protein, human; D025801:Ubiquitin; D016315:Proto-Oncogene Proteins c-abl