eIF-4F and p70S6K play critical roles in translational regulation. eIF-4F is a complex whose functions include the recognition of the mRNA 5’ cap structure (eIF-4E), delivery of an RNA helicase to the 5’ region (eIF-4A), bridging of the mRNA and the ribosome (eIF-4G), and circularization of the mRNA via interaction between eIF-4G and the poly(A) binding protein (PABP). Several stimuli, including growth factors and cytokines, regulate the eIF-4 complex and p70S6K by initiating a phosphorylation cascade involving the sequential activation of PI(3)-K, PDK1/2, Akt/PKB, and FRAP/mTOR kinase. FRAP/mTOR, together with an unidentified kinase, phosphorylates 4E-BP, leading to its dissociation from and activation of eIF-4E. MNK1/2, activated by ERK and p38MAPK, phosphorylates and activates eIF-4E. Both processes contribute to the association of eIF-4E and eIF-4G to form the active eIF-4F complex, a necessary component of the 48S initiation complex. Phosphorylation of ribosomal protein S6 by p70S6K stimulates the translation of mRNAs with a 5' oligopyrimidine tract (5'TOP) which typically encode components of the protein synthesis apparatus.
Copyright © 2001-2014 Daniele Focosi.
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