RNA CUG-binding protein 1 increases translation of 20-kDa isoform of CCAAT/enhancer-binding protein β by interacting with the α and β subunits of eukaryotic initiation translation factor 2
RNA CUG-binding protein 1 increases translation of 20-kDa isoform of CCAAT/enhancer-binding protein β by interacting with the α and β subunits of eukaryotic initiation translation factor 2
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DOI：
10.1074/jbc.m409563200
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发表时间：
2005-05-27
影响因子：
4.8
通讯作者：
Timchenko, LT
中科院分区：
文献类型：
--
作者：
Timchenko, NA;Wang, GL;Timchenko, LT
CCAAT/增强子结合蛋白 (C/EBP beta) 的显性失活 20-kDa 亚型 LIP 在增殖肝脏和肿瘤细胞中表达增加。两种 RNA 结合蛋白 CUGBP1 和钙网蛋白与 C/EBP β 的翻译调节有关。在本文中，我们提出的证据显示了部分肝切除术后肝脏增加 LIP 翻译的几个关键步骤。在部分肝切除术后的早期阶段，肝脏通过过度磷酸化激活 CUGBP1。激活的 CUGBP1 与 C/EBP β mRNA 的 5' 区域结合并取代钙网蛋白，后者部分抑制静止肝脏中 C/EBP β 的翻译。过度磷酸化的 CUGBP1 还与起始因子 eIF2 的 α 和 β 亚基相互作用。我们的数据表明，CUGBP1 与 eIF2 α 的相互作用增强了 CUGBP1 与核糖体的关联，并与部分肝切除术后肝脏中 LIP 翻译的增加相关。我们的数据支持这样的假设：CUGBP1 通过与 eIF2 α 亚基相互作用来增加 LIP 的翻译。这有利于随后招募大量核糖体来启动 LIP 的翻译。
Expression of a dominant negative 20-kDa isoform of CCAAT/enhancer-binding protein (C/EBP beta), LIP, is increased in proliferating livers and in tumor cells. Two RNA-binding proteins, CUGBP1 and calreticulin, have been implicated in the translational regulation of C/EBP beta. In this paper, we present evidence showing several critical steps by which liver increases translation of LIP after partial hepatectomy. At early stages after partial hepatectomy, liver activates CUGBP1 by a hyperphosphorylation. The activated CUGBP1 binds to the 5' region of C/EBP beta mRNA and replaces calreticulin, which partially represses translation of C/EBP beta in quiescent livers. The hyperphosphorylated CUGBP1 also interacts with the alpha and beta subunits of initiation factor eIF2. Our data demonstrate that the interaction of CUGBP1 with the eIF2 alpha enhances the association of CUGBP1 with ribosomes and correlates with increased translation of LIP in the liver after partial hepatectomy. Our data support the hypothesis that CUGBP1 increases translation of LIP by the interaction with the eIF2 alpha subunit. This facilitates subsequent recruitment of larger numbers of ribosomes to initiate translation of LIP.