Mdm2 是 ApoCIII 启动子的新型激活剂，可被 p53 和 SHP 抑制拮抗。
Mdm2 is a novel activator of ApoCIII promoter which is antagonized by p53 and SHP inhibition.
机构信息
Departments of Medicine and Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, United States.
出版信息
Biochem Biophys Res Commun. 2012 Jan 13;417(2):744-6. doi: 10.1016/j.bbrc.2011.12.027. Epub 2011 Dec 16.
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.
摘要
我们研究了 Mdm2 对 ApoCIII 启动子的调节作用及其与 p53 和核受体 SHP 的相互作用。Mdm2 的过表达显著增强了 HNF4α 对 ApoCIII 启动子的活性。通过共免疫沉淀观察到 Mdm2 蛋白与 HNF4α 蛋白的直接结合。p53 的异位表达降低了 HNF4α 对 ApoCIII 启动子的激活作用，并拮抗了 Mdm2 的作用。SHP 的共表达进一步增强了 p53 抑制作用，并消除了 Mdm2 对 ApoCIII 启动子的激活作用。Mdm2 抑制了 p53 介导的 HNF4α 向 ApoCIII 启动子的富集，同时减少了 p53 结合并增加了 SHP 募集到 ApoCIII 启动子。这项研究的结果表明，Mdm2 在调节脂蛋白代谢方面具有潜在的重要功能。
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