title: Mdm2 is a novel activator of ApoCIII promoter which is antagonized by p53 and SHP inhibition.
abstract: 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 HNF4α. A direct association of Mdm2 protein with the HNF4α protein was observed by co-immunoprecipitation. Ectopic expression of p53 decreased HNF4α 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 HNF4α 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.
authors.affiliation: Departments of Medicine and Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, United States.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yang
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
mesh_terms: D053305:Apolipoprotein C-III / Q000037:antagonists & inhibitors / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D053305:Apolipoprotein C-III; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C099713:nuclear receptor subfamily 0, group B, member 2; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2