ERK activation upon hypoxia: involvement in HIF-1 activation

被引:327
作者
Minet, E [1 ]
Arnould, T [1 ]
Michel, G [1 ]
Roland, I [1 ]
Mottet, D [1 ]
Raes, M [1 ]
Remacle, J [1 ]
Michiels, C [1 ]
机构
[1] Fac Univ Notre Dame Paix, Lab Biochim & Biol Cellulaire, B-5000 Namur, Belgium
关键词
hypoxia; hypoxia-inducible factor-1 (HIF-1); extracellular regulated kinase 1 and 2 (ERK);
D O I
10.1016/S0014-5793(00)01181-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 HIT-1 transactivation activity. Moreover, using a kinase assay and Western blot experiments, we showed that HIF-1 alpha 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, (C) 2000 Federation of European Biochemical Societies.
引用
收藏
页码:53 / 58
页数:6
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