Regulation of protein synthesis and the role of eIF3 in cancer
Ribosomes are responsible for translating the information in messenger ribonucleic acids (mRNAs) to synthesise proteins that the cell needs to carry out its function. Protein synthesis begins with the 30S ribosomal subunit recruiting a mRNA with the help of an initiator transfer RNA and three initiation factors. Successful recruitment of the mRNA results in the formation of the 30S pre‐initiation complex, which is followed by the joining of the 50S ribosomal subunit to form the 70S ribosome. Recent studies indicate the order in which the initiation factors bind and promote the steps in initiation complex formation. The formation of the pre‐initiation/initiation complex is often the rate‐limiting step during the process of translation, as it is influenced by a number of translational regulatory mechanisms. As a result, the process of initiation can play a significant role in gene expression.
Regulation of protein synthesis and ..
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Secondary structures at the mRNA ribosomal binding site ..
AB - Eukaryotic initiation factor (eIF) 4E binds to the 5'-cap structure of eukaryotic mRNA and has a central role in the control of cell proliferation. We have shown previously that the stimulation of cultured Xenopus kidney cells with serum resulted in the activation of protein synthesis, enhanced phosphorylation of eIF4E and increased binding of the adapter protein, eIF4G, and poly(A)-binding protein (PABP) to eIF4E to form the functional initiation factor complex, eIF4F/PABP. We now show that cellular stresses such as arsenite, anisomycin and heat shock also result in increased phosphorylation of eIF4E, eIF4F complex formation and the association of PABP with eIF4G, in conditions under which the rate of protein synthesis is severely inhibited. In contrast with reported effects on mammalian cells, the stress-induced increase in eIF4F complex formation occurs in the absence of changes in the association of eIF4E with its binding proteins 4E-BPI or 4E-BP2. The stress-induced changes in eIF4E phosphorylation were totally abrogated by the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580, and were partly inhibited by the phosphoinositide 3-kinase inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin. However, eIF4E phosphorylation was unaffected by extracellular signal-regulated protein kinase (MAP kinase) inhibitor PD98059. These results indicate that cellular stresses activate multiple signalling pathways that converge at the level of eIF4F complex formation to influence the interactions between eIF4E, eIF4G and PABP.
are extremely poor in initiation of protein synthesis, ..
T1 - Cellular stress in Xenopus kidney cells enhances the phosphorylation of eukaryotic translation initiation factor (eIF)4E and the association of eIF4F with poly(A)-binding protein
Protein synthesis and the components of protein …
The final stages of translation termination followed by the subsequent steps involved in the formation of the translation initiation complex. Step 1: dissociation of 70S ribosome into 50S subunit (grey) and 30S subunit (cyan) by ribosome recycling factor (RRF in red) and elongation factor G (EF‐G in yellow); step 2: binding of IF3 in magenta and IF2 in green to the 30S subunit; step 3: binding of IF1 in blue; step 4: binding of fMet‐tRNAfMet (orange linear object); step 5: binding of mRNA (red curved line); step 6: unfolding of mRNA; step 7: interaction of fMet‐tRNAfMet with the mRNA start codon in the P site; step 8: binding of the 50S subunit to the 30S pre‐initiation complex; step 9: dissociation of IF1, IF2 and IF3 from the 70S ribosome.