Mdm2 is a novel activator of ApoCIII promoter which is antagonized by p53 and SHP inhibition

作者：Yang Zhihong; Zhang Yuxia; Wang Li^*

来源：Biochemical and Biophysical Research Communications, 2012, 417(2): 744-746.

DOI：10.1016/j.bbrc.2011.12.027

• Nuclear receptor
• Promoter activity
• Tumor suppressor
• Oncogene
• Lipoprotein

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.

• 出版日期2012-1-13