The deubiquitinating enzyme USP17 is essential for GTPase subcellular localization and cell motility.
The deubiquitinating enzyme USP17 is essential for GTPase subcellular localization and cell motility.
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DOI：
10.1038/ncomms1243
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发表时间：
2011-03-29
影响因子：
16.6
通讯作者：
Johnston, James A.
中科院分区：
文献类型：
--
作者：
de la Vega, Michelle;Kelvin, Alyson A.;Dunican, Dara J.;McFarlane, Cheryl;Burrows, James F.;Jaworski, Jakub;Stevenson, Nigel J.;Dib, Karim;Rappoport, Joshua Z.;Scott, Christopher J.;Long, Aideen;Johnston, James A.
去泛素化酶现在成为控制许多细胞过程的潜在治疗靶点，但很少被证明控制细胞运动。在这里，我们表明，泛素特异性蛋白酶17（USP 17）是快速和短暂诱导的趋化因子SDF-1/CXCL 12和IL-8/CXCL 8在原代细胞和细胞系，它的耗尽完全阻断趋化因子诱导的细胞迁移和细胞骨架重排。使用活细胞成像，我们证明，USP 17是所需的延长和变形虫运动，除了趋化性。先前已经报道USP 17破坏Ras定位，我们现在发现USP 17耗尽阻断趋化因子诱导的GTP酶Cdc 42、Rac和RhoA的亚细胞再定位，这些GTP酶是细胞运动所必需的。总的来说，这些结果表明USP 17在细胞迁移中具有关键作用，并且可能是炎症和转移性疾病的有用药物靶标。去泛素化酶参与多种细胞过程，包括细胞活力。作者揭示了去泛素化酶USP 17在响应趋化因子的细胞迁移中的作用，并表明USP 17是参与细胞运动的GTP酶重新定位所必需的。
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. Deubiquitinating enzymes are involved in multiple cellular processes, including cell viability. The authors reveal a role for the deubiquitinating enzyme, USP17, in the migration of cells in response to chemokines and show that USP17 is required for the relocalization of GTPases involved in cell motility.
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DOI：
10.1083/jcb.200207130
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Maddox AS;Burridge K
通讯作者：
Burridge K
影响因子：
3.7
作者：
Bhavsar, Parag J.;Vigorito, Elena;Ridley, Anne J.
通讯作者：
Ridley, Anne J.
影响因子：
20.3
作者：
Migone, TS;Humbert, M;Johnston, JA
通讯作者：
Johnston, JA
影响因子：
4.8
作者：
de la Vega, Michelle;Burrows, James F.;Johnston, James A.
通讯作者：
Johnston, James A.
影响因子：
5.7
作者：
Colland, Frederic;Formstecher, Etienne;Daviet, Laurent
通讯作者：
Daviet, Laurent