Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric bHLH-PAS protein essential for erythropoietin gene transcription in hypoxic cells. Here we show that both 2-aminopurine and sodium fluoride, inhibitors of serine/threonine kinases and phosphatases, respectively, interfered with the hypoxic induction of HIF-1 DNA-binding activity and expression of HIF-1α and HIF-1β(ARNT) subunits. Genistein, an inhibitor of tyrosine kinases, completely blocked the synthesis of both HIF-1 subunits as well as HIF-1 DNA-binding activity. Sodium orthovanadate, an inhibitor of tyrosine phosphatases increased the basal level of HIF-1 proteins and HIF-1 activity. These data suggest that protein phosphorylation events play an important role in the hypoxia signal-transduction pathway that leads to synthesis of HIF-1α and HIF-1β proteins and the induction of HIF-1 DNA-binding activity.
|Original language||English (US)|
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Jan 1 1995|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology