[Ubiquitination-mediated degradation of epidermal growth factor receptor].
After binding to its ligand, epidermal growth factor receptor (EGFR) dimerizes and is autophosphorylated. These events initiate the signal transduction process, which regulates a plethora of biologic activity. The duration and strength of these signals are controlled by many regulatory mechanisms, including downregulating activated EGFR primarily via endocytosis and ubiquitination-dependent lysomal degradation. The interaction between EGFR and the ubiquitin ligase Cbl/adaptor protein CIN85, as well as ESCRT complex recruitment play important roles in the process of downregulating EGFR. Tumorigenesis results when the de-sensitization process of EGFR is halted by its own mutation or a mutation that abrogates Cbl E3 ligase activity.
Xiu
Xia
X
Department of Radiotherapy, Beijing Hospital, Beijing 100730, China.
Lü
Zhi-min
ZM
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C433810:SH3KBP1 protein, human; D025801:Ubiquitin; D004815:Epidermal Growth Factor; D050721:Proto-Oncogene Proteins c-cbl; D066246:ErbB Receptors; C067419:CBL protein, human; C119570:CBLC protein, human