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

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 Long and James A. Johnston ()
Additional contact information
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

Nature Communications, 2011, vol. 2, issue 1, 1-7

Abstract: 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.

Date: 2011
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms1243 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1243

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1243

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().