4E-BP3 regulates eIF4E-mediated nuclear mRNA export and interacts with replication protein A2.
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.
Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
Chao-Chung
CC
Chen
Jeng-Chang
JC
Lee
Ming-Chung
MC
Chang
D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051716:Replication Protein A / Q000378:metabolism*; D014018:Tissue Distribution
D039561:Eukaryotic Initiation Factor-4E; D012333:RNA, Messenger; D051716:Replication Protein A; D019938:Cyclin D1; C516794:RPA2 protein, human