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
Journal of Biological Chemistry
Expression of a dominant negative 20-kDa isoform of CCAAT/enhancer-binding protein (C/EBP␤), 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␤. 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.
... perphosphorylation. The activated CUGBP1 binds to the 5 region of C/EBP␤ mRNA and replaces calreticulin, which partially represses translation of C/EBP␤ in quiescent livers. The hyperphosphorylated CUGBP1 also interacts with the ␣ and ␤ subunits of initiation factor eIF2. Our data demonstrate that the interaction of CUGBP1 with the eIF2␣ 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␣ subunit. This facilitates subsequent recruitment of larger numbers of ribosomes to initiate translation of LIP.