Inhibition of hypoxia-inducible factor-1alpha (HIF-1alpha) protein synthesis by DNA damage inducing agents.

ABSTRACT: Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor that is composed of a hypoxia-inducible alpha subunit (HIF-1alpha and HIF-2alpha) and a constitutively expressed beta subunit (HIF-1beta). HIF mediates the adaptation of cells and tissues to low oxygen concentrations. It also plays an important role in tumorigenesis and constitutes an important therapeutic target in anti-tumor therapy. We have screened a number of reported HIF inhibitors for their effects on HIF-transcriptional activity and found that the DNA damage inducing agents camptothecin and mitomycin C produced the most robust effects. Camptothecin is a reported inhibitor of HIF-1alpha translation, while mitomycin C has been reported to induce p53-dependent HIF-1alpha degradation. In this study we demonstrate th

SUBMITTER: Lou JJ 

PROVIDER: S-EPMC2866540 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature