Up-regulation of 94-kDa glucose-regulated protein by hypoxia-inducible factor-1 in human endothelial cells in response to hypoxia.

Abstract	Hypoxic environment in solid tumor is known to favor cell survival and to initiate the formation of new capillaries. In this work, we identified by 2D gel analysis 94-kDa glucose-regulated protein (GRP94) as being upregulated in human endothelial cells in response to hypoxia. Three putative hypoxia responsive elements (HRE) were found in the GRP94 promoter. Competition experiments of HIF-1 DNA binding using specific probes containing each HRE sequence of the GRP94 promoter clearly evidenced that HIF-1 binds these sequences with high affinity. The human GRP94 promoter was then cloned upstream of the luciferase gene and showed enhanced activity in hypoxic conditions. Mutation of two of the three HREs present in this promoter completely inhibited the hypoxia-induced increase in luciferase activity.
Authors	Sébastien Paris, Hélène Denis, Edouard Delaive, Marc Dieu, Valéry Dumont, Noëlle Ninane, Martine Raes, Carine Michiels
Journal	FEBS letters (FEBS Lett) Vol. 579 Issue 1 Pg. 105-14 (Jan 03 2005) ISSN: 0014-5793 [Print] England
PMID	15620698 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cell Extracts DNA-Binding Proteins HIF1A protein, human HSP70 Heat-Shock Proteins Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Membrane Proteins Nuclear Proteins RNA, Messenger Transcription Factors glucose-regulated proteins Luciferases
Topics	Base Sequence Cell Extracts (chemistry) Cell Hypoxia Cells, Cultured DNA-Binding Proteins (metabolism) Endothelial Cells (chemistry, metabolism) Gene Expression Genes, Reporter HSP70 Heat-Shock Proteins (analysis, biosynthesis, genetics) Humans Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Luciferases (analysis, genetics) Membrane Proteins (analysis, biosynthesis, genetics) Molecular Sequence Data Mutation (genetics) Nuclear Proteins (metabolism) Promoter Regions, Genetic (genetics) RNA, Messenger (analysis, metabolism) Response Elements (genetics) Transcription Factors (metabolism) Up-Regulation

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