The Translational Regulation in mTOR Pathway

Abstract

The mechanistic/mammalian target of rapamycin (mTOR) plays a master role in cell proliferation and growth in response to insulin, amino acids, energy levels, and oxygen. mTOR can coordinate upstream signals with downstream effectors, including transcriptional and translational apparatuses to regulate fundamental cellular processes such as energy utilization, protein synthesis, autophagy, cell growth, and proliferation. Of the above, protein synthesis is highly energy-consuming; thus, mRNA translation is under the tight and immediate control of mTOR signaling. The translational regulation driven by mTOR signaling mainly relies on eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP), ribosomal protein S6 kinase (S6K), and its downstream players, which are significant in rapid cellular response to environmental change. mTOR signaling not only controls the general mRNA translation, but preferential mRNA translation as well. This means that mTOR signaling shows the stronger selectivity to particular target mRNAs. Some evidence has supported the contribution of 4E-BP and La-related proteins 1 (LARP1) to such translational regulation. In this review, we summarize the mTOR pathway and mainly focus on mTOR-mediated mRNA translational regulation. We introduce the major components of mTOR signaling and their functions in translational control in a general or particular manner, and describe how the specificity of regulation is coordinated. Furthermore, we summarize recent research progress and propose additional ideas for reference. Because the mTOR pathway is on the center of cell growth and metabolism, comprehensively understanding this pathway will contribute to the therapy of related diseases, including cancers, type 2 diabetes, obesity, and neurodegeneration.

Timing of TORC1 inhibition dictates Pol III involvement in longevity inCaenorhabditis elegans

“…To identify these, we tested the genetic interaction of Pol III with candidate mediators implicated in protein synthesis or developmental processes. The ribosomal S6 Kinase (S6K) is a direct target of the TOR kinase and regulates global translation 29,30 . In C. elegans, rsks-1 encodes for S6K and animals lacking this gene are long-lived 31 (Fig.…”

Prospects and hot spots for mammalian target of rapamycin in the field of neuroscience from 2002 to 2021

“…Although the key players, such as 4E-BP, S6K, and LARP1, can explain the major phenomena observed in mTOR translation regulation, there are still some unresolved issues ( Magnuson et al, 2012 ; Castelli et al, 2015 ; Philippe et al, 2020 ; Yang M. et al, 2022 ). For example, not all TOP mRNAs are controlled by 4E-BP, S6K, and LARP1 ( Yang M. et al, 2022 ). This indicates that unknown proteins may be involved in this process.…”

A multi-omics study of the anti-cancer effect of a ferulic acid derivative FA-30

“…Among them, mTOR (mammalian target of rapamycin, mTOR) is particularly important as the core sensing signal of amino acids. 25,26 On one hand, amino acids can regulate the activity of mTOR through a PI3K/AKT-independent pathway. 27 The increased ratio of AMP to ADP can activate AMPK (adenosine 5'-monophosphate (AMP)-activated protein kinase, AMPK), and the activated AMPK can act on TSC1 (Tuberous Sclerosis Complex 1, TSC1)/TSC2 (Tuberous Sclerosis Complex 2, TSC2), thereby inhibiting the activity of mTOR.…”