eIF4E-binding proteins (4E-BPs) are a widespread class of translational regulators that share a canonical (C) eIF4E-binding motif (4E-BM) with eIF4G. Consequently, 4E-BPs compete with eIF4G for binding to the dorsal surface on eIF4E to inhibit translation initiation. Some 4E-BPs contain non-canonical 4E-BMs (NC 4E-BMs), but the contribution of these motifs to the repressive mechanism--and wheth...

Deregulation of protein synthesis is a common event in human cancer and a key player in translational control is eIF4E. Elevated expression levels of eIF4E promote cancer development and progression. Recent findings suggest that eIF4E activity is a key determinant of the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK mediated tumorigenic activity and targeting eIF4E should have a major impact on these pathw...

Advanced breast cancer (eg. stage IV) is resistant to chemotherapy. In this work, we identified potentially druggable targets that are critically involved in chemoresistance. We showed that eIF4E is highly phosphorylated at serine 209 in breast cancer patients in response to chemotherapy, which significantly correlated with poorer clinical responses and outcomes. Depletion of eIF4E enhanced the...

Translational control is a key genetic regulatory mechanism underlying the initial establishment of the major spatial axes of the Drosophila embryo. Many translational control mechanisms target eIF4E (eukaryotic initiation factor 4E), an initiation factor that recognizes the 5'-cap structure of the mRNA. Cap recognition by eIF4E, in complex with eIF4G, is essential for recruitment of the mRNA t...

Eukaryotic translation initiation factor 4E (eIF4E) is the mRNA cap-binding protein required for translation of cellular mRNAs utilizing the 5' cap structure. The rate-limiting factor for mRNA recruitment to ribosomes, eIF4E is a major target for regulation of translation by growth factors, hormones, and other extracellular stimuli. When overexpressed, eIF4E exerts profound effects on cell grow...

Activity-dependent dendritic translation in CNS neurons is important for the synapse-specific provision of proteins that may be necessary for strengthening of synaptic connections. A major rate-limiting factor during protein synthesis is the availability of eukaryotic translation initiation factor 4E (eIF4E), an mRNA 5-cap-binding protein. In this study we show by fluorescence in situ hybridiza...

Eukaryotic initiation factor 4E (eIF4E) controls a crucial step of translation initiation and is critical for cell growth . Biochemical studies have shown that it undergoes a regulated phosphorylation by the MAP-kinase signal-integrating kinases Mnk1 and Mnk2 . Although the role of eIF4E phosphorylation in mammalian cells has remained elusive , recent work in Drosophila has established that it ...

The molecular mechanism underpinning regulation of eukaryotic translation initiation factor eIF4E by 4E-BP1 has remained unclear. We use isothermal calorimetry, circular dichroism, NMR, and computational modeling to analyze how the structure of the eIF4E-binding domain of 4E-BP1 determines its affinity for the dorsal face of eIF4E and thus the ability of this regulator to act as a competitive i...

Accumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent ...

Chronic septic abscess formation causes an inhibition of protein synthesis in gastrocnemius that is not observed in rats with a sterile abscess. The inhibition is associated with an impaired translation initiation. The present study was designed to investigate the effects of sepsis on phosphorylation and availability of eukaryotic initiation factor (eIF)4E in gastrocnemius 5 days after inductio...