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, James A. Johnston

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37 Citations (Scopus)

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.
Original languageEnglish
Article number259
JournalNature Communications
Volume2
Issue number1
DOIs
Publication statusPublished - Mar 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    de la Vega, M., Kelvin, A. A., Dunican, D. J., McFarlane, C., Burrows, J. F., Jaworski, J., Stevenson, N. J., Dib, K., Rappoport, J. Z., Scott, C. J., Long, A., & Johnston, J. A. (2011). The Deubiquitinating Enzyme USP17 is Essential for GTPase Subcellular localization and Cell Motility. Nature Communications, 2(1), [259]. https://doi.org/10.1038/ncomms1243