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An ubiquitination-impaired EGFR mutant was internalized through the clathrin pathway, whereas an EGFR\/ubiquitin chimera, that can signal solely through its ubiquitin (Ub) moiety, was internalized exclusively by the non-clathrin pathway. Non-clathrin internalization of ubiquitinated EGFR depends on its interaction with proteins harboring the Ub-interacting motif, as shown through the ablation of three Ub-interacting motif-containing proteins, eps15, eps15R, and epsin. Thus, eps15s and epsin perform an important function in coupling ubiquitinated cargo to clathrin-independent internalization.<\/jats:p>","DOI":"10.1073\/pnas.0409817102","type":"journal-article","created":{"date-parts":[[2005,2,8]],"date-time":"2005-02-08T23:03:45Z","timestamp":1107903825000},"page":"2760-2765","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":690,"title":["Clathrin-independent endocytosis of ubiquitinated cargos"],"prefix":"10.1073","volume":"102","author":[{"given":"Sara","family":"Sigismund","sequence":"first","affiliation":[{"name":"Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Centre of Cell Oncology and Ultrastructure, Istituto FIRC di Oncologia Molecolare, University of Genoa, Via deToni 14, 16132 Genoa, Italy 16132; European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; and University of Milan, Via di Rudini' 8, 20122 Milan, Italy"}]},{"given":"Tanja","family":"Woelk","sequence":"additional","affiliation":[{"name":"Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Centre of Cell Oncology and Ultrastructure, Istituto FIRC di Oncologia Molecolare, University of Genoa, Via deToni 14, 16132 Genoa, Italy 16132; European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; and University of Milan, Via di Rudini' 8, 20122 Milan, Italy"}]},{"given":"Claudia","family":"Puri","sequence":"additional","affiliation":[{"name":"Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Centre of Cell Oncology and Ultrastructure, Istituto FIRC di Oncologia Molecolare, University of Genoa, Via deToni 14, 16132 Genoa, Italy 16132; European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; and University of Milan, Via di Rudini' 8, 20122 Milan, Italy"}]},{"given":"Elena","family":"Maspero","sequence":"additional","affiliation":[{"name":"Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Centre of Cell Oncology and Ultrastructure, Istituto FIRC di Oncologia Molecolare, University of Genoa, Via deToni 14, 16132 Genoa, Italy 16132; European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; and University of Milan, Via di Rudini' 8, 20122 Milan, Italy"}]},{"given":"Carlo","family":"Tacchetti","sequence":"additional","affiliation":[{"name":"Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Centre of Cell Oncology and Ultrastructure, Istituto FIRC di Oncologia Molecolare, University of Genoa, Via deToni 14, 16132 Genoa, Italy 16132; European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; and University of Milan, Via di Rudini' 8, 20122 Milan, Italy"}]},{"given":"Pietro","family":"Transidico","sequence":"additional","affiliation":[{"name":"Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Centre of Cell Oncology and Ultrastructure, Istituto FIRC di Oncologia Molecolare, University of Genoa, Via deToni 14, 16132 Genoa, Italy 16132; European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; and University of Milan, Via di Rudini' 8, 20122 Milan, Italy"}]},{"given":"Pier Paolo","family":"Di Fiore","sequence":"additional","affiliation":[{"name":"Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Centre of Cell Oncology and Ultrastructure, Istituto FIRC di Oncologia Molecolare, University of Genoa, Via deToni 14, 16132 Genoa, Italy 16132; European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; and University of Milan, Via di Rudini' 8, 20122 Milan, Italy"}]},{"given":"Simona","family":"Polo","sequence":"additional","affiliation":[{"name":"Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Centre of Cell Oncology and Ultrastructure, Istituto FIRC di Oncologia Molecolare, University of Genoa, Via deToni 14, 16132 Genoa, Italy 16132; European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy; and University of Milan, Via di Rudini' 8, 20122 Milan, Italy"}]}],"member":"341","published-online":{"date-parts":[[2005,2,8]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)01681-9"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1124"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(98)01491-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb983"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0854.2003.t01-1-00109.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304474200"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42744-5"},{"key":"e_1_3_2_8_2","unstructured":"Hinrichsen L. 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