Endothelial cells, which line in the interior surface of all blood vessels, are involved in many aspects of physiological and pathological vascular processes, including angiogenesis, inflammation, and atherosclerosis.However, the regulation of endothelial function by ubiquitin-dependent protein degradation remains largely unknown.In this study, we demonstrate FBW7, the substrate-binding subunit of E3 ubiquitin ligase SCFFBw7 (a complex of SKPI-cullin-1-FBW7), plays important roles in endothelial function.