Deubiquitinating Enzyme USP20 Regulates Extracellular Signal-Regulated Kinase 3 Stability and Biological Activity.
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.
['Mathien|Simon|S|', 'Déléris|Paul|P|', 'Soulez|Mathilde|M|', 'Voisin|Laure|L|', 'Meloche|Sylvain|S|']
D002448:Cell Adhesion D045744:Cell Line, Tumor D002465:Cell Movement D000072017:Deubiquitinating Enzymes D057809:HEK293 Cells D019073:HT29 Cells D006367:HeLa Cells D006801:Humans D061986:MCF-7 Cells D048053:Mitogen-Activated Protein Kinase 6 D010766:Phosphorylation D034622:RNA Interference D034741:RNA, Small Interfering D025801:Ubiquitin D043222:Ubiquitin Thiolesterase D054875:Ubiquitination
deubiquitinating enzymes ERK3 MAPKs