mTOR is a central nutrient sensor that signals a cell to grow and proliferate. Through distinct protein complexes it regulates different levels of available cellular energy substrates required for cell growth. One of the important functions of the complex is to maintain available amino acid pool by regulating protein translation. Dysregulation of mTOR pathway leads to aberrant protein translation which manifests into various pathological states. Our review focuses on the role mTOR signaling plays in protein translation and its physiological role. It also throws some light on available data that show translation dysregulation as a cause of pathological complexities like cancer and the available drugs that target the pathway for cancer treatment. 1. Overview of Translation Initiation The regulation of translation is crucial for controlling cell growth and proliferation while translation dysregulation results in aberrant growth and tumorigenicity [1]. Translational control is mediated by the 7-methyl-GTP cap structure present at the 5′ termini of all eukaryotic mRNAs where multiprotein complexes are formed during translation initiation. The eukaryotic initiation factor 4G (eIF4G) acts as a scaffold protein for eukaryotic initiation factor 4E (eIF4E) and eukaryotic initiation factor 4A (eIF4A) to form a protein complex eIF4F, which binds to the cap structure and positions the ribosome near the 5′ terminus of mRNA [2]. Because of its low availability, the cap binding protein eIF4E is the rate limiting factor and inhibitory proteins, namely, eIF4E binding proteins (4E-BPs), regulate this process by binding to eIF4E which prevents its association with eIF4G, thus inhibiting protein translation [3]. Upon mitogenic stimulation 4E-BP1 is phosphorylated which is believed to cause its dissociation from eIF4E leading to the subsequent formation of the eIF4F complex, thus resulting in stimulation of translation initiation. Overall translation levels are therefore lowered when 4E-BP1 is active and this activity is thought to be regulated by mTOR dependent phosphorylation [4]. The mTOR activity itself is regulated by growth factors and amino acid availability as well as the energy status of the cell [4]. When mTOR activity is low, 4E-BP1 is hypophosphorylated which allows it to bind efficiently to eIF4E and block translation initiation whereas when mTOR activity is high, 4E-BP1 is phosphorylated causing it to release eIF4E, thus allowing cap dependent translation to begin [5]. 2. mTOR TOR is the target of rapamycin, a highly conserved serine/threonine kinase that plays
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