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Lookup NU author(s): Professor John LunecORCiD
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The MDM2 oncogene exhibits a complex expression pattern partly due to the usage of multiple promoters. Two MDM2 promoters (P1 and P2) have been identified. P1 is located upstream of exon 1 and is modulated by PTEN. P2 sits in intron 1 and is activated by p53. Here we report the discovery of a third promoter (designated P3) in intron 3 of this gene, which contains a TATA-box element and p53-DNA-binding sequences. DNA-protein binding assays indicated that p53 bound to this region specifically. This region also demonstrated promoter activity in a reporter gene system, which was down-regulated by p53. Furthermore, experiments combining P2 and P3 in the same reporter construct indicated that P3 had a suppressive effect on P2 at high levels of p53. These results suggest that one of the P3 functions is to dampen the expression of MDM2 at high levels of p53, adding an additional element to the feedback loop between p53 and MDM2. © 2005 Elsevier B.V. All rights reserved.
Author(s): Liang, H., Lunec, J.
Publication type: Article
Publication status: Published
Journal: Gene
Year: 2005
Volume: 361
Issue: 1-2
Pages: 112-118
Print publication date: 21/11/2005
ISSN (print): 0378-1119
ISSN (electronic):
URL: http://dx.doi.org/10.1016/j.gene.2005.07.018
DOI: 10.1016/j.gene.2005.07.018
PubMed id: 16202543
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