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https://scholarbank.nus.edu.sg/handle/10635/115909
Title: | Regulation of α-fetoprotein gene expression by antagonism between AP-1 and the glucocorticoid receptor at their overlapping binding site | Authors: | Zhang, X.-K. Dong, J.-M. Chiu, J.-F. |
Issue Date: | 5-May-1991 | Citation: | Zhang, X.-K.,Dong, J.-M.,Chiu, J.-F. (1991-05-05). Regulation of α-fetoprotein gene expression by antagonism between AP-1 and the glucocorticoid receptor at their overlapping binding site. Journal of Biological Chemistry 266 (13) : 8248-8254. ScholarBank@NUS Repository. | Abstract: | We show here that the α-fetoprotein gene (AFP) promoter can be regulated by AP-1 activity using transient transfection assays. AFP promoter activity induced by c-jun/c-fos can be repressed by cotransfected glucocorticoid receptor. The DNA sequence conferring AP-1 activity was located in the proximal promoter region. Gel retardation assays using the AFP proximal promoter identified an AP-1-like sequence which can bind to bacterially expressed c-jun protein. This AP-1-like element, when cloned into the tk promoter, responds to the AP-1 activity of c-jun/c-fos products in both CV-1 and F-9 cells. The element overlaps with a consensus glucocorticoid-responsive element which was shown to confer negative modulation of AFP promoter activity. A 23-base pair DNA element containing the overlapping glucocorticoid-responsive element and AP-1 sites can be positively regulated by glucocorticoid receptor in the absence of c-jun/c-fos products. When plasmids expressing glucocorticoid receptor, c-jun and c-fos are cotransfected together, they repress each other. Thus, these data demonstrate that negative regulation of the AFP gene by glucocorticoid may be due to the interference of AP-1 activity by glucocorticoid receptor either by direct competition for DNA binding or via protein-protein interaction. They provide another example of transcriptional regulation of developing-associated genes between two major signal transduction pathways in response to extracellular stimuli. This supports the model that expression of α-fetoprotein is regulated during development by the effect on transcription of antagonism between glucocorticoid receptor and fos/jun. | Source Title: | Journal of Biological Chemistry | URI: | http://scholarbank.nus.edu.sg/handle/10635/115909 | ISSN: | 00219258 |
Appears in Collections: | Staff Publications |
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