The Von Hippel Lindau (VHL) tumour suppressor protein is a component of a multimeric protein complex VEC, which is an E3 ubiquitin ligase that specifically ubiquitylates the subunit of Hypoxia Inducible Factor (HIF) for subsequent destruction by the 26S proteasome. This establishes VHL as a critical regulator of oxygen-mediated gene expression and a central player in mammalian oxygen sensing. This review will highlight the recent advancements in our understanding of the molecular mechanisms governing the activity of the VEC complex.
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