Hypoxia Inducible Factor 1 Alpha Subunit Inhibitor (HIF1aN)

The deduced 349-amino acid HIF1AN protein is homologous to rat Pass1 and to fly and worm sequences, indicating evolutionary conservation of this protein family. Binding analyses of truncated HIF1AN peptides showed that the inhibitory domain rather than the transactivating domains of HIF1A interacts with HIF1AN, although the presence of TAD-C optimizes binding. Functional analysis indicated that HIAF1AN inhibits HIF1A transcriptional activity in hypoxic and nonhypoxic cells. Further binding analysis determined that the N terminus of HIF1AN interacts with the N terminus of VHL, and that both interact with HIF1A at distinct sites (VHL with TAD-N of HIF1A), allowing the formation of ternary complexes of the 3 proteins.