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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2005-2-21
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pubmed:abstractText |
Hypoxia is a common tumorigenesis enhancer, mostly owing to its impact on gene expression of many angiogenic and invasion-related mediators, some of which are natural substrates for the proprotein convertase furin. Analysis of furin promoters revealed the presence of putative binding sites for hypoxia-inducible factor-1 (HIF-1), a transcription complex that plays a pivotal role in cellular adaptation to hypoxia. In fact, we demonstrate herein that the levels of fur mRNA, encoding furin, are remarkably increased upon hypoxic challenge. Cotransfection of a HIF-1alpha dominant negative form in wild-type (WT) cells or transfection of a furin promoter-reporter gene in HIF-1-deficient cells indicated the requirement of HIF-1 for furin promoter activation by hypoxia. Direct HIF-1 action on the furin promoter was identified as a canonical hypoxia-responsive element site with enhancer capability. The hypoxic/HIF-1 regulation of furin correlated with an increased proteolytic activation of the substrates membrane-type 1 matrix metalloproteinase and transforming growth factor-beta1. Our findings unveil a new facet of the physiological consequences of hypoxia/HIF-1, through enhanced furin-induced proteolytic processing/activation of proproteins known to be involved in tumorigenesis.
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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-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Furin,
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/Matrix Metalloproteinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proprotein Convertases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/TGFB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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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 |
25
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6561-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15611046-Anoxia,
pubmed-meshheading:15611046-Binding Sites,
pubmed-meshheading:15611046-Cell Line, Tumor,
pubmed-meshheading:15611046-DNA-Binding Proteins,
pubmed-meshheading:15611046-Furin,
pubmed-meshheading:15611046-Gene Expression Regulation,
pubmed-meshheading:15611046-Humans,
pubmed-meshheading:15611046-Hypoxia-Inducible Factor 1,
pubmed-meshheading:15611046-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:15611046-Matrix Metalloproteinase 1,
pubmed-meshheading:15611046-Neoplasm Proteins,
pubmed-meshheading:15611046-Nuclear Proteins,
pubmed-meshheading:15611046-Promoter Regions, Genetic,
pubmed-meshheading:15611046-Proprotein Convertases,
pubmed-meshheading:15611046-RNA, Messenger,
pubmed-meshheading:15611046-Transcription Factors,
pubmed-meshheading:15611046-Transcriptional Activation,
pubmed-meshheading:15611046-Transfection,
pubmed-meshheading:15611046-Transforming Growth Factor beta,
pubmed-meshheading:15611046-Transforming Growth Factor beta1
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pubmed:year |
2005
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pubmed:articleTitle |
Hypoxia-enhanced expression of the proprotein convertase furin is mediated by hypoxia-inducible factor-1: impact on the bioactivation of proproteins.
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pubmed:affiliation |
Immunology Division, Pulmonary Division, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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