Linked Life Data

15240563

Source:http://linkedlifedata.com/resource/pubmed/id/15240563

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-8-30
pubmed:abstractText
Activation of the hypoxia-inducible factor alpha-subunits, HIF-1alpha and HIF-2alpha, seems to be subject to similar regulatory mechanisms, and transgene approaches suggested partial functional redundancy. Here, we used RNA interference to determine the contribution of HIF-1alpha vs. HIF-2alpha to the hypoxic gene induction. Surprisingly, most genes tested were responsive only to the HIF-1alpha siRNA, showing no effect by HIF-2alpha knock-down. The same was found for the activation of reporter genes driven by hypoxia-responsive elements (HREs) from the erythropoietin (EPO), vascular endothelial growth factor, or phosphoglycerate kinase gene. Interestingly, EPO was the only gene investigated that showed responsiveness only to HIF-2alpha knock-down, as observed in Hep3B and Kelly cells. In contrast to the EPO-HRE reporter, the complete EPO enhancer displayed dependency on HIF-2alpha regulation, indicating that additional cis-acting elements confer HIF-2alpha specificity within this region. In 786-0 cells lacking HIF-1alpha protein, the identified HIF-1alpha target genes were regulated by HIF-2alpha. Overexpression of the HIFalpha subunits in different cell lines also led to a loss of target gene specificity. In conclusion, we found a remarkably restricted target gene specificity of the HIFalpha subunits, which can be overcome in cells with perturbations in the pVHL/HIF system and under forced expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1462-4
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15240563-Anoxia, pubmed-meshheading:15240563-Basic Helix-Loop-Helix Transcription Factors, pubmed-meshheading:15240563-Cell Line, pubmed-meshheading:15240563-Cell Line, Tumor, pubmed-meshheading:15240563-Enhancer Elements, Genetic, pubmed-meshheading:15240563-Erythropoietin, pubmed-meshheading:15240563-Genes, Reporter, pubmed-meshheading:15240563-Humans, pubmed-meshheading:15240563-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:15240563-Protein Subunits, pubmed-meshheading:15240563-RNA, Messenger, pubmed-meshheading:15240563-RNA, Small Interfering, pubmed-meshheading:15240563-RNA Interference, pubmed-meshheading:15240563-Response Elements, pubmed-meshheading:15240563-Sensitivity and Specificity, pubmed-meshheading:15240563-Trans-Activators, pubmed-meshheading:15240563-Transcription Factors, pubmed-meshheading:15240563-Transcriptional Activation, pubmed-meshheading:15240563-Transfection
pubmed:year
2004
pubmed:articleTitle
Differentiating the functional role of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha (EPAS-1) by the use of RNA interference: erythropoietin is a HIF-2alpha target gene in Hep3B and Kelly cells.
pubmed:affiliation
Department of Nephrology and Medical Intensive Care, Virchow Clinic, Charité University Medicine, Berlin, Germany. christina.warnecke@med4.imed.uni-erlangen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't