Oncotarget

Research Papers:

USP17 is required for clathrin mediated endocytosis of epidermal growth factor receptor

Jakub Jaworski, Michelle de la Vega, Sarah J. Fletcher, Cheryl McFarlane, Michelle K. Greene, Andrew W. Smyth, Sandra Van Schaeybroeck, James A. Johnston, Christopher J. Scott, Joshua Z. Rappoport and James F. Burrows _

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Oncotarget. 2014; 5:6964-6975. https://doi.org/10.18632/oncotarget.2165

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Abstract

Jakub Jaworski1, Michelle de la Vega2, Sarah J. Fletcher3, Cheryl McFarlane2, Michelle K. Greene1, Andrew W. Smyth1, Sandra Van Schaeybroeck4, James A. Johnston2,5, Christopher J. Scott1, Joshua Z. Rappoport3 and James F. Burrows1

1 School of Pharmacy, Queen’s University Belfast, Belfast, UK

2 Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Health Sciences Building, Belfast, UK

3 School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK

4 Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK

5 Current address, Inflammation Research, Amgen Inc., Thousand Oaks, CA

Correspondence:

James F. Burrows, email:

Keywords: Clathrin, Deubiquitinating, Endocytosis, Epidermal growth factor receptor, USP17

Received: May 9, 2014 Accepted: July 2, 2014 Published: July 3, 2014

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.


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