ERK activation upon hypoxia: involvement in HIF-1 activation

E Minet; T Arnould; G Michel; I Roland; D Mottet; M Raes; J Remacle; C Michiels

doi:10.1016/s0014-5793(00)01181-9

ERK activation upon hypoxia: involvement in HIF-1 activation

FEBS Lett. 2000 Feb 18;468(1):53-8. doi: 10.1016/s0014-5793(00)01181-9.

Authors

E Minet¹, T Arnould, G Michel, I Roland, D Mottet, M Raes, J Remacle, C Michiels

Affiliation

¹ Laboratoire de Biochimie et Biologie Cellulaire, Facultés Universitaires de la Paix, 61 rue de Bruxelles, 5000, Namur, Belgium. emmanuel.minet@fundp.ac.be

PMID: 10683440
DOI: 10.1016/s0014-5793(00)01181-9

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blotting, Western
Cell Hypoxia / physiology*
Cell Line
Cell Nucleus / enzymology
DNA-Binding Proteins / metabolism*
Endothelium, Vascular / cytology
Endothelium, Vascular / enzymology
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Flavonoids / pharmacology
Humans
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Microcirculation / cytology
Microcirculation / enzymology
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / metabolism*
Nuclear Proteins / metabolism*
Phosphorylation
Precipitin Tests
Protein Structure, Tertiary
Transcription Factors / metabolism
Tyrosine / metabolism

Substances

DNA-Binding Proteins
Enzyme Inhibitors
Flavonoids
HIF1A protein, human
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Nuclear Proteins
Transcription Factors
Tyrosine
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one