Hypoxia-inducible factor underlies von Hippel-Lindau disease stigmata
- Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Canada
- Department of Biochemistry, Faculty of Medicine, University of Toronto, Canada
Figures
Figure 1
The canonical regulatory components of the metazoan oxygen-sensing pathway.
The dotted line connected to the solved HIFα fragment represents the unstructured C-terminal region of HIFα, which contains the oxygen dependent degradation domain. PDB codes of structures used to construct the protein depictions are 4ZP4 (HIF2α+HIFβ), 4ZPK (HIF2α+HIFβ+Hypoxia-response element), 5L9B (PHD2), 5N4W (Cul2 +Rbx1+EloB + EloC+pVHL), and 3ZRF (EloB +EloC + pVHL). The structural representation of the pVHL-E3 ubiquitin ligase complex was constructed by aligning structures 5N4W and 3ZRF and keeping the most complete model of each duplicated subunit.
Figure 2
HIF-centric unifying model of VHL and other pseudohypoxic diseases.
See text for details. VHL, Elongin B, Elongin C (PDB:1VCB); HIF2α C-Terminal PAS Domain (PDB:3F1P); HIF1α C-Terminal PAS Domain (PDB:4ZPR); PHD2 Catalytic Core (PDB: 5L9B).
Tables
Table 1
VHL disease classification.
| VHL disease | |||||
|---|---|---|---|---|---|
| Type 1 | Type 2A | Type 2B | Type 2C | Type 3 | |
| RCC | + | - | + | - | - |
| Hemangioblastoma | + | + | + | - | - |
| PPGL | - | + | + | + | - |
| Polycythemia | - | - | - | - | + |
Table 2
HIF2-driven disease classification.
| HIF2-driven disease | ||||
|---|---|---|---|---|
| Class 1A | Class 1B | Class 1C | Class 2 | |
| PPGL | + | + | + | - |
| Somatostatinoma | + | - | - | - |
| Polycythemia | + | + | - | + |
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Hypoxia-inducible factor underlies von Hippel-Lindau disease stigmata
eLife 11:e80774.
https://doi.org/10.7554/eLife.80774
