A region between -141 and -61 bp containing a proximal AP-1 is essential for constitutive expression of urokinase-type plasminogen activator receptor.
An 8.5-kb 5'-flanking region of the human urokinase-type plasminogen activator receptor (uPAR) gene was cloned and the detailed uPAR promoter region defined in an 188-bp fragment between bases -141 and +47 relative to the transcription-start site. 5'-Deletion to -100 and -60 in the region abolished its promoter activity, indicating that an 81-bp segment between -141 and -61, which contains a proximal AP-1 site at position -70, is required for uPAR promoter activity. Nuclear extracts from HCT116 cells contain proteins that specifically bind to the AP-1 site. Mutation of the AP-1 motif reduced uPAR promoter activity in comparison with the wild-types. Induction of uPAR expression by phorbol ester requires this AP-1 motif in colon cancer cells. Cotransfection with the c-jun and c-fos expression vectors stimulated the uPAR promoter activity four- to fivefold. These results demonstrate that the proximal AP-1 motif is responsible for approximately 50% of the basal expression of the uPAR gene.
Dang
J
J
Division of Molecular Medicine, John Curtin School of Medical Research, The Australian National University, Canberra.
Boyd
D
D
Wang
H
H
Allgayer
H
H
Doe
W F
WF
Wang
Y
Y
D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D017384:Sequence Deletion; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D018808:Transcription Factor AP-1