Interaction between the VHL tumor suppressor and hypoxia inducible factor, and assay methods relating thereto
First Claim
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1. An assay for a modulator of VHL-HIF α
- subunit interaction, which comprises;
a) bringing into contact a VHL protein, an HIF α
subunit protein and a putative modulator compound under conditions where the VHL protein and the HIF α
subunit protein, in the absence of modulator, are capable of forming a complex; and
b) measuring the degree of inhibition of complex formation caused by said modulator compound.
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Abstract
The invention relates to the finding that the VHL tumour suppressor protein regulates hypoxia inducible factor α subunits, by targeting HIF α for destruction in normoxic, but not hypoxic cells. The invention provides assays for modulators of this interaction, and peptides based upon HIF α subunit sequence which may modulate this interaction.
27 Citations
16 Claims
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1. An assay for a modulator of VHL-HIF α
- subunit interaction, which comprises;
a) bringing into contact a VHL protein, an HIF α
subunit protein and a putative modulator compound under conditions where the VHL protein and the HIF α
subunit protein, in the absence of modulator, are capable of forming a complex; and
b) measuring the degree of inhibition of complex formation caused by said modulator compound. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16)
- subunit interaction, which comprises;
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9. An assay for a modulator which promotes VHL-HIF α
- subunit interaction, which assay comprises;
a) bringing into contact an HIF α
subunit protein and a putative modulator compound in the presence or absence of a VHL protein.b) providing a VHL protein where said protein is absent in step (a); and
c) determining whether the VHL-HIF α
subunit interaction has been promoted by the presence of the modulator.
- subunit interaction, which assay comprises;
Specification