Timchenko Nikolai A, Wang Gou-Li, Timchenko Lubov T
Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA.
J Biol Chem. 2005 May 27;280(21):20549-57. doi: 10.1074/jbc.M409563200. Epub 2005 Mar 23.
Expression of a dominant negative 20-kDa isoform of CCAAT/enhancer-binding protein (C/EBPbeta), 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/EBPbeta. 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/EBPbeta mRNA and replaces calreticulin, which partially represses translation of C/EBPbeta 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 eIF2alpha 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 eIF2alpha subunit. This facilitates subsequent recruitment of larger numbers of ribosomes to initiate translation of LIP.
CCAAT/增强子结合蛋白（C/EBPβ）的显性负性20 kDa亚型LIP在增殖的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，参与了C/EBPβ的翻译调控。在本文中，我们提供证据表明肝脏在部分肝切除术后增加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/EBPβ mRNA的5'区域结合并取代钙网蛋白，钙网蛋白在静止肝脏中部分抑制C/EBPβ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eIF2α的相互作用增强了CUGBP1与核糖体的结合，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，即CUGBP1通过与eIF2α亚基相互作用增加LIP的翻译。这有利于随后招募更多的核糖体来启动LIP的翻译。
