Post-transcriptional regulation of vascular endothelial growth factor by hypoxia - PubMed (original) (raw)

. 1996 Feb 2;271(5):2746-53.

doi: 10.1074/jbc.271.5.2746.

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Post-transcriptional regulation of vascular endothelial growth factor by hypoxia

A P Levy et al. J Biol Chem. 1996.

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Abstract

The major control point for the hypoxic induction of the vascular endothelial growth factor (VEGF) gene is the regulation of the steady-state level of the mRNA. We previously demonstrated a discrepancy between the transcription rate and the steady-state mRNA level induced by hypoxia. This led us to examine the post-transcriptional regulation of VEGF expression. Actinomycin D experiments revealed that hypoxia increased VEGF mRNA half-life from 43 +/- 6 min to 106 +/- 9 min. Using an in vitro mRNA degradation assay, the half-life of VEGF mRNA 3'-untranslated region (UTR) transcripts were also found to be increased when incubated with hypoxic versus normoxic extracts. Both cis-regulatory elements involved in VEGF mRNA degradation under normoxic conditions and in increased stabilization under hypoxic conditions were mapped using this degradation assay. A hypoxia-induced protein(s) was found that bound to the sequences in the VEGF 3'-UTR which mediated increased stability in the degradation assay. Furthermore, genistein, a tyrosine kinase inhibitor, blocked the hypoxia-induced stabilization of VEGF 3'-UTR transcripts and inhibited hypoxia-induced protein binding to the VEGF 3'-UTR. These findings demonstrate a significant post-transcriptional component to the regulation of VEGF.

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