Introduction Initiation of translation in eukaryotes requires the action of at least 33 polypeptides constituting the canonical initiation factors, which act to assemble a series of complexes of increasing size: 43S, 48S and 80S (Kapp and Lorsch, 2004). The rate-limiting step under normal conditions is binding of mRNA to the 43S pre-initiation complex to form the 48S pre-initiation complex. Eff...

The mammalian/mechanistic target of rapamycin (mTOR) is a multifunctional serine/threonine kinase that is hyperactivated in cancer [1]. mTOR forms two distinct complexes, mTORC1 and 2. mTORC1 stimulates translation and perturbs energy metabolism to drive cell proliferation and growth, whereas mTORC2 regulates cytoskeletal organization and cell survival by stimulating AGC kinases (e.g. AKT). The...

Downloa ent advances in understanding the role of eukaryotic translation initiator factor 4E (eIF4E) in igenesis and cancer progression have generated significant interest in therapeutic agents that ctly or directly target aberrant activation of eIF4E in cancer. Here, we address the general function 4E in translation initiation and cancer, present evidence supporting its role in cancer initiati...

Rocaglates are natural products that inhibit protein synthesis in eukaryotes and exhibit antineoplastic activity. In vitro biochemical assays, affinity chromatography experiments coupled with mass spectrometry analysis, and in vivo genetic screens have identified eukaryotic initiation factor (eIF) 4A as a direct molecular target of rocaglates. eIF4A is the RNA helicase subunit of eIF4F, a compl...

Cells respond to environmental stress by inducing translation of a subset of mRNAs important for survival or apoptosis. CHOP, a downstream transcriptional target of stress-induced ATF4, is also regulated translationally in a uORF-dependent manner under stress. Low concentration of anisomycin induces CHOP expression at both transcriptional and translational levels. To study specifically the tran...

Asthma is the most common chronic inflammatory disease of the lung and is characterised by inflammation and airway wall remodelling. Chronic inflammation can be controlled by inhaled antiinflammatory drugs, while airway wall remodelling can only be limited by bronchial thermoplasty. The mechanism that leads to airway wall remodelling is not well understood and recent studies suggested that epig...

Activation of peripheral blood T cells by cross-linking of CD3 results in a rapid and substantial rise in translation rates and proliferation, which coincides with an increase in the cap-binding protein, eIF4E activity. In contrast, immature CD4+ CD8+ double-positive (DP) thymocytes undergo apoptosis in response to anti-CD3 mAb. We have investigated translation initiation in the response of imm...

The viral protein linked to the genome (VPg) of Turnip mosaic virus (TuMV) interacts in vitro with the translation eukaryotic initiation factor (eIF) 4E. In the present study, we investigated the consequence of TuMV infection on eIF4E expression. Two isomers are present in plants, namely eIF4E and eIF(iso)4E. Expression of the latter was detected in both TuMV-infected and mock-inoculated Brassi...

Nuclear localization of β-catenin is essential for the progression of various human cancers via transcriptional upregulation of downstream genes. The MAP kinase interacting serine/threonine kinase (MNK)-eukaryotic translation initiation factor 4E (eIF4E) axis has been reported to activate Wnt/β-catenin signaling, and CGP57380, an inhibitor of MNK kinases, inhibits the proliferation of multiple ...

The eukaryotic translation initiation factor 4E (eIF4E) is considered as a key survival protein involved in cell cycle progression, transformation and apoptosis resistance. Herein, we demonstrate that medicinal plant derivative 3-AWA (from Withaferin A) suppressed the proliferation and metastasis of CaP cells through abrogation of eIF4E activation and expression via c-FLIP dependent mechanism. ...