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Cited by 635

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Induction of Endothelial PAS Domain Protein-1 by Hypoxia: Characterization and Comparison With Hypoxia-Inducible Factor-1α

Open access
Wiesener, M.S., Turley, H., Allen, W.E., Willam, C., Eckardt, K.-U., Talks, K.L., Wood, S.M., Gatter, K.C., Harris, A.L., Pugh, C.W., Ratcliffe, P.J., Maxwell, P.H.·1998·Blood
DOI 10.1182/blood.v92.7.2260
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Abstract

Hypoxia results in adaptive changes in the transcription of a range of genes including erythropoietin. An important mediator is hypoxia-inducible factor-1 (HIF-1), a DNA binding complex shown to contain at least two basic helix-loop-helix PAS-domain (bHLH-PAS) proteins, HIF-1α and aryl hydrocarbon nuclear receptor translocator (ARNT). In response to hypoxia, HIF-1α is activated and accumulates rapidly in the cell. Endothelial PAS domain protein 1 (EPAS-1) is a recently identified bHLH-PAS protein with 48% identity to HIF-1α, raising the question of its role in responses to hypoxia. We developed specific antibodies and studied expression and regulation of EPAS-1 mRNA and protein across a range of human cell lines. EPAS-1 was widely expressed, and strongly induced by hypoxia at the level of protein but not mRNA. Comparison of the effect of a range of activating and inhibitory stimuli showed striking similarities in the EPAS-1 and HIF-1α responses. Although major differences were observed in the abundance of EPAS-1 and HIF-1α in different cell types, differences in the inducible response were subtle with EPAS-1 protein being slightly more evident in normoxic and mildly hypoxic cells. Functional studies in a mutant cell line (Ka13) expressing neither HIF-1α nor EPAS-1 confirmed that both proteins interact with hypoxically responsive targets, but suggest target specificity with greater EPAS-1 transactivation (relative to HIF-1α transactivation) of the VEGF promoter than the LDH-A promoter.

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Metadata

Authors
Wiesener, M. S., Turley, H., Allen, W. E., Willam, C., Eckardt, K.-U., Talks, K. L., Wood, S. M., Gatter, K. C., Harris, A. L., Pugh, C. W., Ratcliffe, P. J., & Maxwell, P. H.
Venue
Blood
Publisher
American Society of Hematology
Published
1998-10-01
Volume
92
Issue
7
Pages
2260-2268
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v92.7.2260
OpenAlex
W1844723954
Cited by
635
References
4
FWCI
11.65
Type
journal article
Language
en
Open access
bronze

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