Mdm2 is a novel activator of ApoCIII promoter which is antagonized by p53 and SHP inhibition.
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.
Mesh Terms:
Apolipoprotein C-III, HeLa Cells, Humans, Promoter Regions, Genetic, Proto-Oncogene Proteins c-mdm2, Receptors, Cytoplasmic and Nuclear, Trans-Activators, Transcriptional Activation, Tumor Suppressor Protein p53
Apolipoprotein C-III, HeLa Cells, Humans, Promoter Regions, Genetic, Proto-Oncogene Proteins c-mdm2, Receptors, Cytoplasmic and Nuclear, Trans-Activators, Transcriptional Activation, Tumor Suppressor Protein p53
Biochem. Biophys. Res. Commun.
Date: Jan. 13, 2012
PubMed ID: 22197810
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