Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2000-10-27
pubmed:abstractText
Prolonged serum deprivation induces a structurally and functionally contractile phenotype in about 1/6 of cultured airway myocytes, which exhibit morphological elongation and accumulate abundant contractile apparatus-associated proteins. We tested the hypothesis that transcriptional activation of genes encoding these proteins accounts for their accumulation during this phenotypic transition by measuring the transcriptional activities of the murine SM22 and human smooth muscle myosin heavy chain promoters during transient transfection in subconfluent, serum fed or 7 day serum-deprived cultured canine tracheal smooth muscle cells. Contrary to our expectation, SM22 and smooth muscle myosin heavy chain promoter activities (but not viral murine sarcoma virus-long terminal repeat promoter activity) were decreased in long term serum-deprived myocytes by at least 8-fold. Because serum response factor (SRF) is a required transcriptional activator of these and other smooth muscle-specific promoters, we evaluated the expression and function of SRF in subconfluent and long term serum-deprived cells. Whole cell SRF mRNA and protein were maintained at high levels in serum-deprived myocytes, but SRF transcription-promoting activity, nuclear SRF binding to consensus CArG sequences, and nuclear SRF protein were reduced. Furthermore, immunocytochemistry revealed extranuclear redistribution of SRF in serum-deprived myocytes; nuclear localization of SRF was restored after serum refeeding. These results uncover a novel mechanism for physiological control of smooth muscle-specific gene expression through extranuclear redistribution of SRF and consequent down-regulation of its transcription-promoting activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30387-93
pubmed:dateRevised
2011-11-10
pubmed:meshHeading
pubmed-meshheading:10866994-Animals, pubmed-meshheading:10866994-Biological Transport, pubmed-meshheading:10866994-Cell Compartmentation, pubmed-meshheading:10866994-Cell Nucleus, pubmed-meshheading:10866994-Culture Media, Serum-Free, pubmed-meshheading:10866994-Cytoplasm, pubmed-meshheading:10866994-DNA-Binding Proteins, pubmed-meshheading:10866994-Dogs, pubmed-meshheading:10866994-Down-Regulation, pubmed-meshheading:10866994-Gene Expression Regulation, pubmed-meshheading:10866994-Microfilament Proteins, pubmed-meshheading:10866994-Muscle, Smooth, pubmed-meshheading:10866994-Muscle Proteins, pubmed-meshheading:10866994-Myosin Heavy Chains, pubmed-meshheading:10866994-Nuclear Proteins, pubmed-meshheading:10866994-Promoter Regions, Genetic, pubmed-meshheading:10866994-Serum Response Factor, pubmed-meshheading:10866994-Trachea, pubmed-meshheading:10866994-Transcription Factor AP-2, pubmed-meshheading:10866994-Transcription Factors
pubmed:year
2000
pubmed:articleTitle
Physiological control of smooth muscle-specific gene expression through regulated nuclear translocation of serum response factor.
pubmed:affiliation
Department of Medicine, University of Chicago, University of Chicago, Chicago, Illinois 60637, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't