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The deubiquitinating enzyme USP17 is essential for GTPase subcellular localization and cell motility

Author

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  • Michelle de la Vega

    (Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences)

  • Alyson A. Kelvin

    (Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences)

  • Dara J. Dunican

    (Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.)

  • Cheryl McFarlane

    (Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences)

  • James F. Burrows

    (Queen's University Molecular Therapeutics, School of Pharmacy, Queen's University)

  • Jakub Jaworski

    (Queen's University Molecular Therapeutics, School of Pharmacy, Queen's University)

  • Nigel J. Stevenson

    (Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences)

  • Karim Dib

    (Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences)

  • Joshua Z. Rappoport

    (School of Biosciences, University of Birmingham, Edgbaston)

  • Christopher J. Scott

    (Queen's University Molecular Therapeutics, School of Pharmacy, Queen's University)

  • Aideen Long

    (Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.)

  • James A. Johnston

    (Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences)

Abstract

Deubiquitinating enzymes are now emerging as potential therapeutic targets that control many cellular processes, but few have been demonstrated to control cell motility. Here, we show that ubiquitin-specific protease 17 (USP17) is rapidly and transiently induced in response to chemokines SDF-1/CXCL12 and IL-8/CXCL8 in both primary cells and cell lines, and that its depletion completely blocks chemokine-induced cell migration and cytoskeletal rearrangements. Using live cell imaging, we demonstrate that USP17 is required for both elongated and amoeboid motility, in addition to chemotaxis. USP17 has previously been reported to disrupt Ras localization and we now find that USP17 depletion blocks chemokine-induced subcellular relocalization of GTPases Cdc42, Rac and RhoA, which are GTPases essential for cell motility. Collectively, these results demonstrate that USP17 has a critical role in cell migration and may be a useful drug target for both inflammatory and metastatic disease.

Suggested Citation

  • Michelle de la Vega & Alyson A. Kelvin & Dara J. Dunican & Cheryl McFarlane & James F. Burrows & Jakub Jaworski & Nigel J. Stevenson & Karim Dib & Joshua Z. Rappoport & Christopher J. Scott & Aideen L, 2011. "The deubiquitinating enzyme USP17 is essential for GTPase subcellular localization and cell motility," Nature Communications, Nature, vol. 2(1), pages 1-7, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1243
    DOI: 10.1038/ncomms1243
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    Cited by:

    1. Shu Fan Zhou & Singaram Gopalakrishnan & Yuan Hao Xu & Jie Yang & Yun Wah Lam & Stella W Pang, 2016. "A Unidirectional Cell Switching Gate by Engineering Grating Length and Bending Angle," PLOS ONE, Public Library of Science, vol. 11(1), pages 1-18, January.

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