Linked Life Data

9748288

Source:http://linkedlifedata.com/resource/pubmed/id/9748288

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
40
pubmed:dateCreated
1998-11-12
pubmed:abstractText
The transcription rates of glycolytic enzyme genes are coordinately induced when cells are exposed to low oxygen tension. This effect has been described in many cell types and is not restricted to species or phyla. In mammalian cells, there are 11 distinct glycolytic enzymes, at least 9 of which are induced by hypoxia. Recent reports described a role for the hypoxia-inducible factor-1 (HIF-1) in the transcriptional activation of lactate dehydrogenase A, aldolase-A, phosphoglycerate kinase, and enolase-1 genes. It is not known whether the HIF-1 factor acts exclusively to regulate these genes during hypoxia, or how the other genes of the pathway are regulated. In this paper, we describe analyses of the muscle-specific pyruvate kinase-M and beta-enolase promoters that implicate additional mechanisms for the regulation of glycolytic enzyme gene transcription by hypoxia. Transient transcription of a reporter gene directed by either promoter was activated when transfected muscle cells were exposed to hypoxia. Neither of these promoters contain HIF-1 binding sites. Instead, the hypoxia response was localized to a conserved GC-rich element positioned immediately upstream of a GATAA site in the proximal promoter regions of both genes. The GC element was essential for both basal and hypoxia-induced expression and bound the transcription factors Sp1 and Sp3. Hypoxia caused the progressive depletion of Sp3 determined by DNA binding studies and Western analyses, whereas Sp1 protein levels remained unchanged. Overexpression of Sp3 repressed expression of beta-enolase promoters. It is concluded that hypoxia activates these glycolytic enzyme gene promoters by down-regulating Sp3, thereby removing the associated transcriptional repression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26087-93
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9748288-Anoxia, pubmed-meshheading:9748288-Base Sequence, pubmed-meshheading:9748288-Binding Sites, pubmed-meshheading:9748288-Cells, Cultured, pubmed-meshheading:9748288-Conserved Sequence, pubmed-meshheading:9748288-DNA-Binding Proteins, pubmed-meshheading:9748288-Down-Regulation, pubmed-meshheading:9748288-Gene Expression Regulation, pubmed-meshheading:9748288-Genes, Reporter, pubmed-meshheading:9748288-Glycolysis, pubmed-meshheading:9748288-Hypoxia-Inducible Factor 1, pubmed-meshheading:9748288-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:9748288-Molecular Sequence Data, pubmed-meshheading:9748288-Muscles, pubmed-meshheading:9748288-Nuclear Proteins, pubmed-meshheading:9748288-Phosphopyruvate Hydratase, pubmed-meshheading:9748288-Promoter Regions, Genetic, pubmed-meshheading:9748288-Pyruvate Kinase, pubmed-meshheading:9748288-Repressor Proteins, pubmed-meshheading:9748288-Sp1 Transcription Factor, pubmed-meshheading:9748288-Sp3 Transcription Factor, pubmed-meshheading:9748288-Transcription Factors, pubmed-meshheading:9748288-Transfection
pubmed:year
1998
pubmed:articleTitle
Hypoxia regulates beta-enolase and pyruvate kinase-M promoters by modulating Sp1/Sp3 binding to a conserved GC element.
pubmed:affiliation
Department of Molecular and Cellular Pharmacology, University of Miami Medical Center, Miami, Florida 33136, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't