Deubiquitinating Enzyme USP20 Regulates Extracellular Signal-Regulated Kinase 3 Stability and Biological Activity
| Autor: | Mathilde Soulez, Simon Mathien, Laure Voisin, Sylvain Meloche, Paul Déléris |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Regulator Actin cytoskeleton organization Deubiquitinating enzyme 03 medical and health sciences Ubiquitin Cell Movement Cell Line Tumor Cell Adhesion Humans Phosphorylation RNA Small Interfering Protein kinase A Molecular Biology Mitogen-Activated Protein Kinase 6 biology Deubiquitinating Enzymes Kinase Effector Ubiquitination Cell Biology Cell biology 030104 developmental biology HEK293 Cells biology.protein MCF-7 Cells RNA Interference HT29 Cells Ubiquitin Thiolesterase Research Article HeLa Cells |
| Popis: | Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK) whose regulatory mechanisms and biological functions remain superficially understood. Contrary to most protein kinases, ERK3 is a highly unstable protein that is subject to dynamic regulation by the ubiquitin-proteasome system. However, the effectors that control ERK3 ubiquitination and degradation are unknown. In this study, we carried out an unbiased functional loss-of-function screen of the human deubiquitinating enzyme (DUB) family and identified ubiquitin-specific protease 20 (USP20) as a novel ERK3 regulator. USP20 interacts with and deubiquitinates ERK3 both in vitro and in intact cells. The overexpression of USP20 results in the stabilization and accumulation of the ERK3 protein, whereas USP20 depletion reduces the levels of ERK3. We found that the expression levels of ERK3 correlate with those of USP20 in various cellular contexts. Importantly, we show that USP20 regulates actin cytoskeleton organization and cell migration in a manner dependent on ERK3 expression. Our results identify USP20 as a bona fide regulator of ERK3 stability and physiological functions. |
| Databáze: | OpenAIRE |
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