Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-10-15
pubmed:abstractText
To elucidate the mechanism(s) by which adrenocorticotropic hormone (corticotropin) stimulates transcription of the steroid 11beta-monooxygenase gene (CYP11B1) in adrenocortical cells, the 5'-flanking region of rat CYP11B1 was analyzed using transient transfection and protein-binding assays with mouse adrenocortical Y1 cells. The results indicated that both basal and corticotropin-induced transcriptional activation of CYP11B1 required a common regulatory element containing a binding site for activator protein-1 (AP-1) transcription factors (dimers of the Jun and Fos family proteins) in the 5'-flanking region. Other DNA-binding protein(s) such as transcription factor Ad4BP was not required for either basal or corticotropin-induced transcriptional activation. Corticotropin stimuli were found to induce expression of a subset of the jun and fos family gene products in Y1 cells significantly, while total amounts of AP-1 factors capable of binding to its site in the CYP11B1 promoter did not change greatly. Treatment of rats with corticotropin had similar effects on mRNA levels of the jun and fos family genes in the adrenocortical zona fasciculata cells together with an enhancing effect on the level of CYP11B1 mRNA in the tissue. The effects of corticotropin on mRNA levels of the jun and fos family genes as well as transcription of CYP11B1 in Y1 cells were mimicked by treatment of the cells with dibutyryl cAMP. Furthermore, when components of AP-1 factors were overexpressed by transfecting Y1 cells with their expression vectors, a paired expression of AP-1 components such as c-Jun and c-Fos, which were inducible by corticotropin, transactivated the CYP11B1 promoter more strongly in the absence of corticotropin than other combinations such as JunD and Fra-2 expressed constitutively. These results suggest that corticotropin regulates transcription of the CYP11B1 gene by causing compositional changes in AP-1 transcription factors in the adrenocortical cells via a cAMP-dependent pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
256
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
190-200
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9746364-Adrenal Cortex, pubmed-meshheading:9746364-Adrenocorticotropic Hormone, pubmed-meshheading:9746364-Animals, pubmed-meshheading:9746364-Binding Sites, pubmed-meshheading:9746364-Bucladesine, pubmed-meshheading:9746364-DNA Mutational Analysis, pubmed-meshheading:9746364-Dimerization, pubmed-meshheading:9746364-Genes, Reporter, pubmed-meshheading:9746364-Genes, fos, pubmed-meshheading:9746364-Genes, jun, pubmed-meshheading:9746364-Mice, pubmed-meshheading:9746364-Promoter Regions, Genetic, pubmed-meshheading:9746364-Protein Binding, pubmed-meshheading:9746364-RNA, Messenger, pubmed-meshheading:9746364-Rats, pubmed-meshheading:9746364-Sequence Deletion, pubmed-meshheading:9746364-Steroid 11-beta-Hydroxylase, pubmed-meshheading:9746364-Transcription, Genetic, pubmed-meshheading:9746364-Transcription Factor AP-1, pubmed-meshheading:9746364-Transcriptional Activation, pubmed-meshheading:9746364-Transfection, pubmed-meshheading:9746364-Zona Fasciculata
pubmed:year
1998
pubmed:articleTitle
Adrenocorticotropic hormone stimulates CYP11B1 gene transcription through a mechanism involving AP-1 factors.
pubmed:affiliation
Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't