scholarly journals Transcriptional Up-regulation of Inhibitory PAS Domain Protein Gene Expression by Hypoxia-inducible Factor 1 (HIF-1)

2007 ◽  
Vol 282 (19) ◽  
pp. 14073-14082 ◽  
Author(s):  
Yuichi Makino ◽  
Rie Uenishi ◽  
Kensaku Okamoto ◽  
Tsubasa Isoe ◽  
Osamu Hosono ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Gene ◽  
Hypoxia Inducible Factor ◽  
Pas Domain ◽  
Hypoxia Inducible Factor 1 ◽  
Domain Protein

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

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2260-2268 ◽  
Author(s):  
M.S. Wiesener ◽  
H. Turley ◽  
W.E. Allen ◽  
C. Willam ◽  
K.-U. Eckardt ◽  
...  
Keyword(s):  
Mutant Cell ◽  
Hypoxia Inducible Factor ◽  
Cell Types ◽  
Pas Domain ◽  
Functional Studies ◽  
Hypoxia Inducible Factor 1 ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon ◽  
Domain Protein ◽  
Different Cell Types

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.

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

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2260-2268 ◽  
Author(s):  
M.S. Wiesener ◽  
H. Turley ◽  
W.E. Allen ◽  
C. Willam ◽  
K.-U. Eckardt ◽  
...  
Keyword(s):  
Mutant Cell ◽  
Hypoxia Inducible Factor ◽  
Cell Types ◽  
Pas Domain ◽  
Functional Studies ◽  
Hypoxia Inducible Factor 1 ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon ◽  
Domain Protein ◽  
Different Cell Types

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.

scholarly journals Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth

1997 ◽  
Vol 94 (15) ◽  
pp. 8104-8109 ◽  
Author(s):  
P. H. Maxwell ◽  
G. U. Dachs ◽  
J. M. Gleadle ◽  
L. G. Nicholls ◽  
A. L. Harris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Solid Tumors ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1
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