title: USP17 is required for clathrin mediated endocytosis of epidermal growth factor receptor.
abstract: Previously we have shown that expression of the deubiquitinating enzyme USP17 is required for cell proliferation and motility. More recently we reported that USP17 deubiquitinates RCE1 isoform 2 and thus regulates the processing of 'CaaX' motif proteins. Here we now show that USP17 expression is induced by epidermal growth factor and that USP17 expression is required for clathrin mediated endocytosis of epidermal growth factor receptor. In addition, we show that USP17 is required for the endocytosis of transferrin, an archetypal substrate for clathrin mediated endocytosis, and that USP17 depletion impedes plasma membrane recruitment of the machinery required for clathrin mediated endocytosis. Thus, our data reveal that USP17 is necessary for epidermal growth factor receptor and transferrin endocytosis via clathrin coated pits, indicate this is mediated via the regulation of the recruitment of the components of the endocytosis machinery and suggest USP17 may play a general role in receptor endocytosis.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Jakub
authors.initials: J
authors.lastname: Jaworski
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Health Sciences Building, Belfast, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: de la Vega
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Fletcher
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Health Sciences Building, Belfast, UK.
authors.forename: Cheryl
authors.initials: C
authors.lastname: McFarlane
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Greene
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Smyth
authors.affiliation: Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Van Schaeybroeck
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Health Sciences Building, Belfast, UK; Current address, Inflammation Research, Amgen Inc., Thousand Oaks, CA.
authors.forename: James A
authors.initials: JA
authors.lastname: Johnston
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Scott
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Rappoport
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: James F
authors.initials: JF
authors.lastname: Burrows
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D002966:Clathrin; D025801:Ubiquitin; C512478:EGFR protein, human; D066246:ErbB Receptors; D010450:Endopeptidases; C484854:USP17L2 protein, human