Co-localization of elements required for phorbol ester stimulation and glucocorticoid repression of proliferin gene expression.
Proliferin (PLF) gene expression provides a model of growth-related transcriptional activation in mouse cells. Transcription from a cloned PLF promoter is inducible by phorbol esters, and this induction involves a region of 31 bp that includes an AP-1 site and a cluster of sites similar to the simian virus 40 (SV40) SphI element. The mutation of either the AP-1 or the SphI sites abolishes phorbol ester induction, and the transfer of this 31-bp sequence to a site upstream of a minimal promoter is sufficient to confer phorbol-ester responsiveness. In contrast to phorbol esters, glucocorticoids repress PLF transcription, which results in a reduced accumulation of PLF mRNA in serum-stimulated cells. Repression is dependent on the glucocorticoid receptor, which binds to the PLF promoter in a region that includes the AP-1 site, and the 31-bp phorbol ester 12-O-tetra decanoylphorbol-13-acetate (TPA)-inducible region is sufficient to mediate glucocorticoid repression. In addition, extracts from glucocorticoid-treated and untreated mouse cells are found to differ in the nature of the protein complexes that interact with the AP-1 site.
Mordacq
J C
JC
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208.
Linzer
D I
DI
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D007739:L Cells; D008969:Molecular Sequence Data; D010053:Ovary; D011388:Prolactin; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C000634106:Prl2c2 protein, mouse; D011993:Recombinant Fusion Proteins; D003907:Dexamethasone; D011388:Prolactin; D013755:Tetradecanoylphorbol Acetate