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

M de la Vega; AA Kelvin; DJ Dunican; C McFarlane; JF Burrows; J Jaworski; NJ Stevenson; K Dib; Joshua Rappoport; CJ Scott; A Long; JA Johnston

doi:10.1038/ncomms1243

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

M de la Vega, AA Kelvin, DJ Dunican, C McFarlane, JF Burrows, J Jaworski, NJ Stevenson, K Dib, Joshua Rappoport, CJ Scott, A Long, JA Johnston

Biosciences

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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 language	English
Pages (from-to)	259
Number of pages	1
Journal	Nature Communications
Volume	2
DOIs	https://doi.org/10.1038/ncomms1243
Publication status	Published - 1 Mar 2011

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title = "The deubiquitinating enzyme USP17 is essential for GTPase subcellular localization and cell motility",

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.",

author = "{de la Vega}, M and AA Kelvin and DJ Dunican and C McFarlane and JF Burrows and J Jaworski and NJ Stevenson and K Dib and Joshua Rappoport and CJ Scott and A Long and JA Johnston",

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doi = "10.1038/ncomms1243",

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TY - JOUR

T1 - The deubiquitinating enzyme USP17 is essential for GTPase subcellular localization and cell motility

AU - de la Vega, M

AU - Kelvin, AA

AU - Dunican, DJ

AU - McFarlane, C

AU - Burrows, JF

AU - Jaworski, J

AU - Stevenson, NJ

AU - Dib, K

AU - Rappoport, Joshua

AU - Scott, CJ

AU - Long, A

AU - Johnston, JA

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms1243

DO - 10.1038/ncomms1243

M3 - Article

SN - 2041-1723

VL - 2

SP - 259

JO - Nature Communications

JF - Nature Communications

ER -

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

Abstract

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