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Target intelligence / Profile preview
Von Hippel-Lindau E3 Ubiquitin Ligase (VHL)
- Target
- VHL
- Molecular classification
- E3 Ubiquitin Ligase, Tumor Suppressor, Protein Complex Subunit
01
Overview
The von Hippel-Lindau (VHL) protein is an E3 ubiquitin ligase that functions as part of a multi-protein complex (VCB-CUL2 complex). It plays a critical role in regulating cellular responses to oxygen levels by targeting hypoxia-inducible factors (HIFs) for degradation under normoxic conditions. Loss or mutation of VHL leads to increased risk for several cancers and syndromic conditions. It has become an important target for PROTAC development to induce targeted protein degradation.
- Other names
- VHL tumor suppressorVHL proteinVCB-CUL2 complex
02
Mechanism of action
Recruitment of target protein to VHL E3 ligase complex for ubiquitination and subsequent proteasomal degradation.
03
Biological functions
UbiquitinationProtein DegradationRegulation of Hypoxia ResponseTranscriptional RegulationCell Proliferation ControlExtracellular Matrix Maintenance
04
Disease associations
Cancervon Hippel-Lindau DiseaseRenal Cell CarcinomaPheochromocytomaParaganglioma
05
Safety considerations
Off-target effects of VHL-targeting PROTACsUnintended degradation of other proteinsPotential for drug resistance
06
Interacting drugs
PROTACs (VHL-based)
1 more in the full profile.
07
Biomarkers
HIF-1α levelsHIF-2α levelsVHL mutation status
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