factor inhibiting HIF-1

FIH1 (Factor Inhibiting HIF-1), also known as HIF1AN, is an asparagine hydroxylase enzyme that serves as a critical negative regulator of the hypoxia-inducible factor 1-alpha (HIF-1α) and NOTCH signaling pathways. Encoded by the *HIF1AN* gene, FIH1 hydroxylates a specific asparagine residue in the C-terminal transactivation domain of HIF-1α, preventing its association with transcriptional co-activators and thereby suppressing the expression of pro-angiogenic genes such as VEGF-A. In glioblastoma (GBM), the FIH1 locus on chromosome 10q24 is frequently deleted, suggesting a tumor-protective role. Therapeutic strategies under investigation, notably at institutions like UTHealth Houston, involve the reconstitution or overexpression of FIH1 to inhibit tumor angiogenesis and Notch-mediated progression. Preclinical studies have demonstrated that FIH1 overexpression, particularly when combined with oncolytic herpes simplex virus (oHSV) therapy, can reduce vascular permeability, decrease angiogenesis markers, and improve survival in intracranial tumor models.

Other names

HIF1A asparagine hydroxylaseHIF-1A asparagine hydroxylaseHIF 1A asparagine hydroxylasehypoxia-inducible factor 1-alpha inhibitor