4E-BP3 regulates eIF4E-mediated nuclear mRNA export and interacts with replication protein A2

• Published in: FEBS letters 2012-07, Vol.586 (16), p.2260-2266
• Main Authors: Chen, Chao-Chung, Lee, Jeng-Chang, Chang, Ming-Chung
• Format: Article
• Language: English
• Subjects: 4E-BP3; Active Transport, Cell Nucleus; Cell Line, Tumor; Cell Nucleus - metabolism; Cyclin D1 - metabolism; Cytoplasm - metabolism; DNA Damage; DNA Replication; eIF4E; Eukaryotic Initiation Factor-4E - metabolism; Eukaryotic Initiation Factor-4E - physiology; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Models, Biological; mRNA export; Phosphorylation; Protein Structure, Tertiary; Replication Protein A - metabolism; RNA, Messenger - metabolism; RPA2; Tissue Distribution
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2012.05.059

► We found 4E-BP3 acts as an inhibitor of eIF4E-mediated mRNA export. ► 4E-BP3 interacts with dephosphorylated form of RPA2, and could not interact with phosphorylated form of RPA2. ► The inhibition ability of 4E-BP3 on eIF4E-mediated mRNA export is regulated by the phosphorylation state of RPA2. In nucleus, eIF4E regulates the nucleus export of specific mRNA. In this study, altered 4E-BP3 (eIF4E-binding protein 3) expression resulted in profoundly affected cyclin D1 protein levels, partially due to changes in the cytoplasmic cyclin D1 mRNA levels in both U2OS and MCF7 cells, whereas altered 4E-BP1 expression did not affect eIF4E-mediated cyclin D1 mRNA export. 4E-BP3 also affected a subset of growth promoting mRNAs exported in an eIF4-dependent manner. Furthermore, 4E-BP3 interacted with dephosphorylated RPA2 (replication protein A2). The results indicated 4E-BP3 acts as an inhibitor of eIF4E-mediated mRNA export in the examined cells, and 4E-BP3 inhibition of eIF4E-mediated mRNA export is regulated by the phosphorylation state of RPA2. 4EBP3 physically interacts with RPA2 by anti bait coimmunoprecipitation (View interaction)