Oocyte meiotic spindles are associated with spindle-enriched mRNAs, phosphorylated ribosome protein S6, and phosphorylated variants of the key translational regulator, eukaryotic translation initiation factor 4E-binding protein 1 (eIF4E-BP1), consistent with translational control of localized mRNAs by eIF4E-BP1 in facilitating spindle formation and stability. Using specific kinase inhibitors, w...

Cell signaling pathways and protein translation are crucial for understanding malignant transformation. 4E-BP1 and the eIF4F complex regulate cap-dependent translation. We investigated how 4E-BP1 and eIF4E phosphorylation status affects in vitro and in vivo cell proliferation in a breast cancer model. Cells from 2 breast carcinoma lines (MDA-MB 231 and MDA-MB 468) and human fibroblasts (IMR90 c...

The overexpression of eukaryotic initiation factor 4E (eIF4E), a key regulator of protein synthesis, is involved in the malignant progression of various human cancers. We investigated eIF4E expression in atypical adenomatous hyperplasia (AAH) and adenocarcinomas of the human peripheral lung. On the basis of the WHO criteria with minor modifications, adenocarcinomas were classified as bronchiolo...

Abstract Objective: Phosphorylated Eukaryotic translation initiation factor 4E (p-eIF4E) is a critical regulator of protein synthesis and phosphorylated by MNK1/2 to promote the mRNA subset. We have shown that blocking eIF4E phosphorylation increased anti-tumor immune response, especially CD8 T cell activation. However, role p-eIF4E in CD4 subsets, particular regulatory cells (Tregs) still unkn...

The eukaryotic initiation factor 4G (eIF4G) is the core of a multicomponent switch controlling gene expression at the level of translation initiation. It interacts with the small ribosomal subunit interacting protein, eIF3, and the eIF4E/cap-mRNA complex in order to load the ribosome onto mRNA during cap-dependent translation. We describe the solution structure of the complex between yeast eIF4...

Rapamycin, a potential anti-cancer agent, modulates activity of various factors functioning in translation, including eIF4E, an initiation factor selectively regulating expression of a subset of cellular transcripts. We show here that rapamycin suppresses levels of the p53-regulator MDM2 by translational inhibition without affecting mdm2 mRNA expression or protein stability. Rapamycin inhibits ...

Assembly of the eIF4E/eIF4G complex has a central role in the regulation of gene expression at the level of translation initiation. This complex is regulated by the 4E-BPs, which compete with eIF4G for binding to eIF4E and which have tumor-suppressor activity. To pharmacologically mimic 4E-BP function we developed a high-throughput screening assay for identifying small-molecule inhibitors of th...

Ribosomal attachment to mammalian capped mRNAs is achieved through the cap-eukaryotic initiation factor 4E (eIF4E)-eIF4G-eIF3-40S chain of interactions, but the mechanism by which mRNA enters the mRNA-binding channel of the 40S subunit remains unknown. To investigate this process, we recapitulated initiation on capped mRNAs in vitro using a reconstituted translation system. Formation of initiat...

Patients with esophageal squamous cell cancer are often diagnosed with advanced diseases that respond poorly to chemotherapy. Overexpression of eIF4E leads to enhance the translation of key malignancy-related proteins and enabling tumor growth and chemoresistance in a variety of human malignancies, but whether it has a role in ESCC remains obscure. We hypothesized that eIF4E promoted ESCC tumor...

T he PI3K/Akt/mTORC1 axis is perhaps the most frequently activated pathway in human cancers. Therefore, concerted efforts are being made to inhibit this pathway pharmacologically for cancer therapy. Although some success has been achieved, the multiple feedback loops that “litter” this pathway (ref. 1; Fig. 1), combined with the potential toxicity resulting from its inhibition, make the pharmac...