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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2004-4-6
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pubmed:abstractText |
Hypoxia plays a key role in the pathophysiology of many disease states, and expression of the retinoic acid receptor-related orphan receptor alpha (RORalpha) gene increases under hypoxia. We investigated the mechanism for this transient hypoxia-induced increase in RORalpha expression. Reverse transcription-coupled PCR analysis revealed that the steady-state level of mRNA for the RORalpha4 isoform, but not the RORalpha1 isoform, increased in HepG2 cells after 3 h of hypoxia. Transient transfection studies showed that the hypoxia-induced increase in RORalpha4 mRNA occurs at the transcriptional level and is dependent on a hypoxia-responsive element (HRE) located downstream of the promoter. A dominant-negative mutant of hypoxia-inducible factor-1alpha (HIF-1alpha) abrogates the transcription activated by hypoxia as well as the transcription activated by exogenously expressed HIF-1alpha, demonstrating the direct involvement of HIF-1alpha in the transcriptional activation. However, HIF-1 alone was not sufficient to activate transcription in hypoxic conditions but, rather, required Sp1/Sp3, which binds to a cluster of GC-rich sequences adjacent to the HRE. Deletion of one or more of these GC boxes reduced or eliminated the HIF-1-dependent transcription. Together, these results suggest that the hypoxia-responsive region of the RORalpha4 promoter is composed of the HRE and GC-rich sequences and that the transcriptional activation under hypoxia is conferred through the cooperation of HIF-1 with Sp1/Sp3.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 1...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/ROR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RORA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Tyrosine Kinase-like...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/SP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sp3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15025-31
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14742449-Anoxia,
pubmed-meshheading:14742449-Cell Line,
pubmed-meshheading:14742449-DNA,
pubmed-meshheading:14742449-DNA-Binding Proteins,
pubmed-meshheading:14742449-Gene Deletion,
pubmed-meshheading:14742449-HeLa Cells,
pubmed-meshheading:14742449-Humans,
pubmed-meshheading:14742449-Hypoxia-Inducible Factor 1,
pubmed-meshheading:14742449-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:14742449-Nuclear Proteins,
pubmed-meshheading:14742449-Nuclear Receptor Subfamily 1, Group F, Member 1,
pubmed-meshheading:14742449-Plasmids,
pubmed-meshheading:14742449-Promoter Regions, Genetic,
pubmed-meshheading:14742449-Protein Isoforms,
pubmed-meshheading:14742449-RNA, Messenger,
pubmed-meshheading:14742449-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:14742449-Receptor Tyrosine Kinase-like Orphan Receptors,
pubmed-meshheading:14742449-Receptors, Cell Surface,
pubmed-meshheading:14742449-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:14742449-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:14742449-Sp1 Transcription Factor,
pubmed-meshheading:14742449-Sp3 Transcription Factor,
pubmed-meshheading:14742449-Time Factors,
pubmed-meshheading:14742449-Trans-Activators,
pubmed-meshheading:14742449-Transcription, Genetic,
pubmed-meshheading:14742449-Transcription Factors,
pubmed-meshheading:14742449-Transcriptional Activation,
pubmed-meshheading:14742449-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
Hypoxia-induced activation of the retinoic acid receptor-related orphan receptor alpha4 gene by an interaction between hypoxia-inducible factor-1 and Sp1.
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pubmed:affiliation |
Laboratory of Genomics and Proteomics, Faculty of Pharmacy and Pharmaceutical Science, Fukuyama University, 1 Gakuen-cho, Fukuyama 729-0292, Japan.
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pubmed:publicationType |
Journal Article
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