The tumour suppressor HACE1 controls cell migration by regulating Rac1 degradation.
作者： S Castillo-Lluva , C-T Tan , M Daugaard , P H B Sorensen , A Malliri
DOI: 10.1038/ONC.2012.189
关键词:
摘要: The small GTPase Rac1 is a key regulator of cell motility. Multiple mechanisms regulate activity including its ubiquitylation and subsequent degradation. Here, we identify the tumour suppressor HACE1 (HECT domain Ankyrin repeat Containing E3 ubiquitin-protein ligase 1) as an ubiquitin responsible for degradation following activation by migration stimulus. We show that interaction enhanced hepatocyte growth factor (HGF) signalling, Rac activator potent stimulus migration. Furthermore, catalyses poly-ubiquitylation at lysine 147 HGF, resulting in proteasomal This negative feedback mechanism likely restricts Consistent with this, depletion accompanied increased total levels accumulation membrane ruffles. Moreover, HACE1-depletion enhances independently stimulation, which may have significance malignant conversion. A non-ubiquitylatable rescues defect Rac1-null cells to greater extent than wild-type Rac1. These findings antagonist through ability degrade active
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