mTORC1-Mediated Control of Protein Translation

Dempsey, Jamie M.; Mahoney, Sarah J.; Blenis, John

doi:10.1016/s1874-6047(10)28001-0

Cited by 6 publications

(7 citation statements)

References 104 publications

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“…Increased mTOR Complex 1 (mTORC1) activity results in higher global protein expression, and inappropriate levels of activity have been linked to several kinds of cancer [35] . Phosphorylation of ribosomal protein S6 (pS6) is a downstream indicator of mTORC1 activity [36] , whilst phosphorylation of the proline-rich Akt Substrate (PRAS) is an upstream indicator of mTORC1 activity, with PRAS acting to inhibit mTORC1 [37] . mTOR Complex 2 (mTORC2) regulates cytoskeletal organization and turnover as well as AKT phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

Alteration of Cellular Behavior and Response to PI3K Pathway Inhibition by Culture in 3D Collagen Gels

et al. 2012

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Most investigations into cancer cell drug response are performed with cells cultured on flat (2D) tissue culture plastic. Emerging research has shown that the presence of a three-dimensional (3D) extracellular matrix (ECM) is critical for normal cell behavior including migration, adhesion, signaling, proliferation and apoptosis. In this study we investigate differences between cancer cell signaling in 2D culture and a 3D ECM, employing real-time, live cell tracking to directly observe U2OS human osteosarcoma and MCF7 human breast cancer cells embedded in type 1 collagen gels. The activation of the important PI3K signaling pathway under these different growth conditions is studied, and the response to inhibition of both PI3K and mTOR with PI103 investigated. Cells grown in 3D gels show reduced proliferation and migration as well as reduced PI3K pathway activation when compared to cells grown in 2D. Our results quantitatively demonstrate that a collagen ECM can protect U2OS cells from PI103. Overall, our data suggests that 3D gels may provide a better medium for investigation of anti-cancer drugs than 2D monolayers, therefore allowing better understanding of cellular response and behavior in native like environments.

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Section: Introductionmentioning

confidence: 99%

Alteration of Cellular Behavior and Response to PI3K Pathway Inhibition by Culture in 3D Collagen Gels

et al. 2012

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“…However, its interaction with kinases and putative response to phosphorylation is complex. Human eEF2K has been shown to be part of the mTOR signaling pathway and is phosphorylated by multiple kinases with differing effects on eEF2K function, including AMPK which activates and S6K which is inhibitory [ 82 , 83 ]. Despite the many published p-sites on the human homolog, Pt_eEF2K p-site Ser-1214 is not conserved between P. tricornutum and human eEF2K.…”

Section: Resultsmentioning

confidence: 99%

The Importance of Protein Phosphorylation for Signaling and Metabolism in Response to Diel Light Cycling and Nutrient Availability in a Marine Diatom

Tan

Smith

Hixson

et al. 2020

Biology

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Diatoms are major contributors to global primary production and their populations in the modern oceans are affected by availability of iron, nitrogen, phosphate, silica, and other trace metals, vitamins, and infochemicals. However, little is known about the role of phosphorylation in diatoms and its role in regulation and signaling. We report a total of 2759 phosphorylation sites on 1502 proteins detected in Phaeodactylum tricornutum. Conditionally phosphorylated peptides were detected at low iron (n = 108), during the diel cycle (n = 149), and due to nitrogen availability (n = 137). Through a multi-omic comparison of transcript, protein, phosphorylation, and protein homology, we identify numerous proteins and key cellular processes that are likely under control of phospho-regulation. We show that phosphorylation regulates: (1) carbon retrenchment and reallocation during growth under low iron, (2) carbon flux towards lipid biosynthesis after the lights turn on, (3) coordination of transcription and translation over the diel cycle and (4) in response to nitrogen depletion. We also uncover phosphorylation sites for proteins that play major roles in diatom Fe sensing and utilization, including flavodoxin and phytotransferrin (ISIP2A), as well as identify phospho-regulated stress proteins and kinases. These findings provide much needed insight into the roles of protein phosphorylation in diel cycling and nutrient sensing in diatoms.

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“…[14a] Tr anslation is ac omplex process which involves many factors,f or example,e IFs,e EFs,a nd other biomolecules related to regulation pathways.T he focus of recent research has progressed from manipulating physical interactions between nanomaterials and biomolecules (e.g.m RNAa nd ribosome proteins) for translation initiation to regulating translation in specific cells.F or instance,the mechanistic target of rapamycin complex 1( mTORC1) is the major signaling pathway responsible for the phosphorylation of several proteins or substrates relevant to translation. [23] Thep otential of mTORC1 for enhanced mRNAt ranslation was implicated by Sahay et al Theupstream effector of mTORC1, tuberous sclerosis complex 2, was inhibited to activate mTORC1 for enhanced mRNAt ranslation to protein. [24] Considering that glutathione (GSH) depletion upregulated mTORC1 and celltype-dependent differences in GSH levels, [25a,b] cell-specific biochemistry-modulated translation could be an ew concept to improve protein expression efficacy.…”

Section: Regulating Cell-specific Translation Pathwaysmentioning

confidence: 99%

Emerging Concepts of Nanobiotechnology in mRNA Delivery

Wang

2020

Angew Chem Int Ed

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Introducing mRNA into cells has attracted intense interest for diverse applications; however, success requires delivery solutions. Engineered nanomaterials have been applied as mRNA nanocarriers; their functions are designed mainly as delivery vehicles, but rarely in regulation of the protein translation. Recently, progress in nanobiotechnology has shifted the design principle of mRNA nanocarriers from simple delivery tools to translation modulators. Here, we review the emerging concepts of nanomaterials regulating mRNA translation and recent progress in mRNA delivery. Designer nanomaterials providing integrated functions for specific mRNA applications are also reviewed to provide insights for the design of next‐generation nanomaterials to revolutionize mRNA technology.

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mTORC1-Mediated Control of Protein Translation

Cited by 6 publications

References 104 publications

Alteration of Cellular Behavior and Response to PI3K Pathway Inhibition by Culture in 3D Collagen Gels

Alteration of Cellular Behavior and Response to PI3K Pathway Inhibition by Culture in 3D Collagen Gels

The Importance of Protein Phosphorylation for Signaling and Metabolism in Response to Diel Light Cycling and Nutrient Availability in a Marine Diatom

Emerging Concepts of Nanobiotechnology in mRNA Delivery

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