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FEBS Lett. 2000 Feb 18;468(1):53-8.

ERK activation upon hypoxia: involvement in HIF-1 activation.

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Laboratoire de Biochimie et Biologie Cellulaire, Facult├ęs Universitaires de la Paix, 61 rue de Bruxelles, 5000, Namur, Belgium.


Hypoxia-inducible factor-1 (HIF-1) is a transcription factor activated by hypoxia. The HIF-1 activation transduction pathway is poorly understood. In this report, we investigated the activation of extracellular regulated kinases (ERK) in hypoxia and their involvement in HIF-1 activation. We demonstrated that in human microvascular endothelial cells-1 (HMEC-1), ERK kinases are activated during hypoxia. Using dominant negative mutants, we showed that ERK1 is needed for hypoxia-induced HIF-1 transactivation activity. Moreover, using a kinase assay and Western blot experiments, we showed that HIF-1alpha is phosphorylated in hypoxia by an ERK-dependent pathway. These results evidence the role of mitogen-activated protein kinase in the transcriptional response to hypoxia.

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