Linked Life Data

10542274

Source:http://linkedlifedata.com/resource/pubmed/id/10542274

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
1999-12-13
pubmed:databankReference
pubmed:abstractText
Caveolin-1 is a principal component of caveolae membranes in vivo. Caveolin-1 mRNA and protein expression are down-regulated in NIH 3T3 cells in response to transformation by activated oncogenes, such as H-Ras(G12V) and v-Abl. The mechanisms governing this down-regulation event remain unknown. Here, we show that caveolin-1 gene expression is directly regulated by activation of the Ras-p42/44 MAP kinase cascade. Down regulation of caveolin-1 protein expression by Ras is independent of (i) the type of activating mutation (G12V versus Q61L) and (ii) the form of activated Ras transfected (H-Ras versus K-Ras versus N-Ras). Treatment of Ras or Raf-transformed NIH 3T3 cells with a well characterized MEK inhibitor (PD 98059) restores caveolin-1 protein expression. In contrast, treatment of v-Src and v-Abl transformed NIH 3T3 cells with PD 98059 does not restore caveolin-1 expression. Thus, there must be at least two pathways for down-regulating caveolin-1 expression: one that is p42/44 MAP kinase-dependent and another that is p42/44 MAP kinase-independent. We focused our efforts on the p42/44 MAP kinase-dependent pathway. The activity of a panel of caveolin-1 promoter constructs was evaluated using transient expression in H-Ras(G12V) transformed NIH 3T3 cells. We show that caveolin-1 promoter activity is up-regulated approximately 5-fold by inhibition of the p42/44 MAP kinase cascade. Using electrophoretic mobility shift assays we provide evidence that the caveolin-1 promoter (from -156 to -561) is differentially bound by transcription factors in normal and H-Ras(G12V)-transformed cells. We also show that activation of protein kinase A (PKA) signaling is sufficient to down-regulate caveolin-1 protein expression and promoter activity. Thus, we have identified two signaling pathways (Ras-p42/44 MAP kinase and PKA) that transcriptionally down-regulate caveolin-1 gene expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32333-41
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10542274-3T3 Cells, pubmed-meshheading:10542274-Animals, pubmed-meshheading:10542274-Caveolin 1, pubmed-meshheading:10542274-Caveolins, pubmed-meshheading:10542274-Cell Transformation, Viral, pubmed-meshheading:10542274-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:10542274-Down-Regulation, pubmed-meshheading:10542274-Enzyme Activation, pubmed-meshheading:10542274-Gene Expression Regulation, pubmed-meshheading:10542274-Membrane Proteins, pubmed-meshheading:10542274-Mice, pubmed-meshheading:10542274-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:10542274-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:10542274-Mitogen-Activated Protein Kinases, pubmed-meshheading:10542274-Molecular Sequence Data, pubmed-meshheading:10542274-Promoter Regions, Genetic, pubmed-meshheading:10542274-Signal Transduction, pubmed-meshheading:10542274-Transcription Factors
pubmed:year
1999
pubmed:articleTitle
p42/44 MAP kinase-dependent and -independent signaling pathways regulate caveolin-1 gene expression. Activation of Ras-MAP kinase and protein kinase a signaling cascades transcriptionally down-regulates caveolin-1 promoter activity.
pubmed:affiliation
Department of Molecular Pharmacology, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't