期刊
DEVELOPMENTAL CELL
卷 21, 期 5, 页码 959-965出版社
CELL PRESS
DOI: 10.1016/j.devcel.2011.08.015
关键词
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资金
- Conseil Regional PACA
- Conseil General des Alpes-Maritimes
- INSERM
- Fondation Infectiopole Sud
- Agence Nationale de la Recherche [ANR-07-MIME-007, ANR-07-BLAN-0046]
- Association pour la Recherche sur le Cancer (ARC) [4906]
- Ligue Nationale Contre le Cancer
- Agence Nationale de la Recherche (ANR) [ANR-07-BLAN-0046] Funding Source: Agence Nationale de la Recherche (ANR)
Rac1 small GTPase controls essential aspects of cell biology and is a direct target of numerous bacterial virulence factors. The CNF1 toxin of pathogenic Escherichia coli addresses Rac1 to ubiq uitin-proteasome system (UPS). We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rad to UPS. HACE1 binds preferentially GTP-bound Rad and catalyzes its polyubiquitylation. HACE1 expression increases the ubiquitylation of Rac1, when the GTPase is activated by point mutations or by the GEF-domain of Dbl. RNAi-mediated depletion of HACE1 blocks the ubiquitylation of active Rac1 and increases GTP-bound Racl cellular levels. HACE1 antagonizes cell isotropic spreading, a hallmark of Rac1 activation, and is required for endothelial cell monolayer invasion by bacteria. Together, these data establish the role of the HACE1 E3 ubiquitin-ligase in controlling Rac1 ubiquitylation and activity.
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