The VHL complex is a multi-subunit ubiquitin ligase composed of VHL, Elongin B, Elongin C, Cul2 and Rbx1. The VHL protein serves as the substrate recognition component and is linked by Elongin C to a heterodimeric Cul2/Rbx1 module that functions as a potent activator of the ubiquitination of target proteins by an E2 conjugating enzyme. Elongin B interacts with the complex through Elongin C and appears to stabilize the binding of Elongin C to VHL. The primary function of the VHL complex is to regulate HIF (hypoxia inducible factor) activity by targeting the hydroxylated HIF-1α subunit for ubiquitination and rapid proteasomal degradation under normoxic conditions. It therefore plays an important role in the regulation of hypoxia-inducible genes such as the vascular endothelial growth factor (VEGF) and glucose transport-1 (Glut-1). Mutations in VHL are associated with the inherited von Hippel-Lindau (VHL) cancer syndrome and numerous forms of renal cell carcinoma.
Ubiquitination Cascade Comoponent: E3
Purified using glutathione sepharose.
For Specific Activity data, refer to the Certificate of Analysis for individual lots of this enzyme.
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