Effect of Protein Kinase and Phosphatase Inhibitors on Expression of Hypoxia Inducible Factor 1

作者：G.L. Wang, Bing‐Hua Jiang, Gregg L. Semenza · 发表于：Biochemical and Biophysical Research Communications · 年份：1995 · DOI：10.1006/bbrc.1995.2674 · 被引用次数：230 · 研究领域：Cancer, Hypoxia, and Metabolism、Metabolism, Diabetes, and Cancer、Autophagy in Disease and Therapy

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-1 alpha and HIF-1 beta(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-1 alpha and HIF-1 beta proteins and the induction of HIF-1 DNA-binding activity.