HIF-1 alpha
3 important questions on HIF-1 alpha
Explain the HIFalpha (TF) pathway.
When there O2.
When there is low O2.
- HIF-apha is made but degraded.
- Degradation via PHD's => prolyl-4-hydroxylates => hydroxylation (OH toevoegen)
- Recognition by VHL
- Ubiquination
When there is low O2.
- PHD not active
- No hydroxylation
- HIF-alpha active
- To the nucleus => heterodimer with ARNT.
- Binding to a HRE = hypoxia response element.
Where does the hydroxylation occur?What type of degradation occurs with O2?
Hydroxylation on a specific proline residue. Proteasomal degradation.
What is the relation with propyl-4-hydroxylase inhibition?
HIF-alpha won't be degraded => upreagulated HIF.
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