期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 417, 期 2, 页码 744-746出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2011.12.027
关键词
Nuclear receptor; Promoter activity; Tumor suppressor; Oncogene; Lipoprotein
资金
- National Institutes of Health [T32CA092347, DK080440]
We examined the effect of Mdm2 on regulation of the ApoCIII promoter and its cross-talk with p53 and nuclear receptor SHP. Overexpression of Mdm2 markedly enhanced ApoCIII promoter activity by HNF4 alpha. A direct association of Mdm2 protein with the HNF4 alpha protein was observed by co-immunoprecipitation. Ectopic expression of p53 decreased HNF4 alpha activation of the ApoCIII promoter and antagonized the effect of Mdm2. Co-expression of SHP further strengthened p53 inhibition and abolished Mdm2 activation of the ApoCIII promoter. Mdm2 inhibited p53-mediated enrichment of HNF4 alpha to the ApoCIII promoter while simultaneously reducing p53 binding and increasing recruitment of SHP to the ApoCIII promoter. The results from this study implicate a potentially important function of Mdm2 in regulation of lipoprotein metabolism. (C) 2011 Elsevier Inc. All rights reserved.
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