Linked Life Data

12569082

Source:http://linkedlifedata.com/resource/pubmed/id/12569082

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-5-8
pubmed:abstractText
Hepatocyte growth factor (HGF) receptor, the product of the c-met protooncogene, is transcriptionally regulated by a wide variety of cytokines as well as extracellular environmental cues. In this report, we demonstrate that c-met expression was significantly suppressed by oxidative stress. Treatment of mouse renal inner medullary collecting duct epithelial cells with 0.5 mM H(2)O(2) inhibited c-met mRNA and protein expression, which was concomitant with induction of Egr-1 transcription factor. Ectopic expression of Egr-1 in renal epithelial cells markedly inhibited endogenous c-met expression in a dose-dependent fashion, suggesting a causative effect of Egr-1 in mediating c-met suppression. The cis-acting element responsible for H(2)O(2)-induced c-met inhibition was localized at nucleotide position -223 to -68 of c-met promoter, in which reside an imperfect Egr-1 and three Sp1-binding sites. Egr-1 markedly suppressed c-met promoter activity but did not directly bind to its cis-acting element in the c-met gene. Induction of Egr-1 by oxidative stress attenuated the binding of Sp1 to its cognate sites, but it did not affect Sp1 abundance in renal epithelial cells. Immunoprecipitation uncovered that Egr-1 physically interacted with Sp1 by forming the Sp1/Egr-1 complex, which presumably resulted in a decreased availability of unbound Sp1 as a transcriptional activator for the c-met gene. Thus it appears that inhibition of c-met expression by oxidative stress is mediated by the interplay between Sp1 and Egr-1 transcription factors. Our findings reveal a novel transcriptional regulatory mechanism by which Egr-1 sequesters Sp1 as a transcriptional activator of c-met via physical interaction.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1931-857X
pubmed:author
pubmed:issnType
Print
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F1216-25
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed-meshheading:12569082-Animals, pubmed-meshheading:12569082-Blotting, Northern, pubmed-meshheading:12569082-Cell Line, pubmed-meshheading:12569082-Cells, Cultured, pubmed-meshheading:12569082-DNA, pubmed-meshheading:12569082-DNA-Binding Proteins, pubmed-meshheading:12569082-Early Growth Response Protein 1, pubmed-meshheading:12569082-Electrophoretic Mobility Shift Assay, pubmed-meshheading:12569082-Gene Expression Regulation, pubmed-meshheading:12569082-Immediate-Early Proteins, pubmed-meshheading:12569082-Kidney, pubmed-meshheading:12569082-Luciferases, pubmed-meshheading:12569082-Mice, pubmed-meshheading:12569082-Nuclear Proteins, pubmed-meshheading:12569082-Oxidative Stress, pubmed-meshheading:12569082-Plasmids, pubmed-meshheading:12569082-Precipitin Tests, pubmed-meshheading:12569082-Proto-Oncogene Proteins c-met, pubmed-meshheading:12569082-RNA, pubmed-meshheading:12569082-RNA, Messenger, pubmed-meshheading:12569082-Transcription Factors, pubmed-meshheading:12569082-Transfection
pubmed:year
2003
pubmed:articleTitle
Suppression of HGF receptor gene expression by oxidative stress is mediated through the interplay between Sp1 and Egr-1.
pubmed:affiliation
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.