mTORC1 Links Protein Quality and Quantity Control by Sensing Chaperone Availability
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TLDR
It is demonstrated that cells distinguish moderate reductions in protein quality from severe protein misfolding using molecular chaperones to differentially regulate mTORC1 signaling, and the tight linkage between protein quality and quantity control provides a plausible mechanism coupling protein mis folding with metabolic dyshomeostasis.About:
This article is published in Journal of Biological Chemistry.The article was published on 2010-08-27 and is currently open access. It has received 50 citations till now. The article focuses on the topics: Hsp33 & Chaperone (protein).read more
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Journal ArticleDOI
TORC1‐mediated sensing of chaperone activity alters glucose metabolism and extends lifespan
Matea Perić,Anita Lovrić,Ana Šarić,Marina Musa,Peter Bou Dib,Marina Rudan,Andrea Nikolić,Sandra Sobočanec,Ana Matea Mikecin,Sven Dennerlein,Ira Milosevic,Kristian Vlahoviček,Nuno Raimundo,Anita Krisko +13 more
TL;DR: The results set a novel paradigm for the role of proteostasis in aging: modulation of the misfolded protein level can affect cellular metabolic features as well as mitochondrial activity and consequently modify lifespan.
Journal ArticleDOI
β-Secretase 1’s Targeting Reduces Hyperphosphorilated Tau, Implying Autophagy Actors in 3xTg-AD Mice
Diego Piedrahita,John Fredy Castro-Alvarez,Ryan L. Boudreau,Andres Villegas-Lanau,Kenneth S. Kosik,Juan Carlos Gallego-Gómez,Gloria Patricia Cardona-Gómez +6 more
TL;DR: It is suggested that BACE1 silencing neuroprotects reducing soluble hyperphosphorylated tau, modulating certain autophagy-related proteins in aged 3xTg-AD mice.
Journal ArticleDOI
The role of mTOR in age-related diseases.
TL;DR: A review of recent insights into the mTOR signalling pathway, including its regulation and its influence on various hallmarks of ageing at the cellular level is provided in this article, where the authors provide an overview of the recent insights.
Journal ArticleDOI
Direct imaging of the recruitment and phosphorylation of S6K1 in the mTORC1 pathway in living cells.
Abdullah R. Ahmed,Raymond J. Owens,Raymond J. Owens,Christopher D. Stubbs,Anthony W. Parker,Richard B. Hitchman,Rahul B. Yadav,Maud Dumoux,Chris Hawes,Stanley W. Botchway +9 more
TL;DR: It is demonstrated how FRET-FLIM imaging technology can be used to show localisation of S6K1 phosphorylation in living cells and hence a key site of action of inhibitors targeting mTOR phosphorylated cells.
Journal ArticleDOI
Therapeutic Manipulation of Ageing: Repurposing Old Dogs and Discovering New Tricks.
Venkatesh Mallikarjun,Joe Swift +1 more
TL;DR: This review summarises a sample of the most promising efforts to deliver the products of ageing research to the clinic as well as the development of novel therapeutics to target ageing.
References
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Journal ArticleDOI
TOR signaling in growth and metabolism.
TL;DR: The physiological consequences of mammalianTORC1 dysregulation suggest that inhibitors of mammalian TOR may be useful in the treatment of cancer, cardiovascular disease, autoimmunity, and metabolic disorders.
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Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
David E. Harrison,Randy Strong,Zelton D Sharp,James F. Nelson,Clinton M. Astle,Kevin Flurkey,Nancy L. Nadon,J. Erby Wilkinson,Krystyna Frenkel,Christy S. Carter,Christy S. Carter,Marco Pahor,Marco Pahor,Martin A. Javors,Elizabeth Fernandez,Richard A. Miller +15 more
TL;DR: It is reported that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age.
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mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery
Do Hyung Kim,Dos D. Sarbassov,Siraj M. Ali,Jessie E. King,Robert R. Latek,Hediye Erdjument-Bromage,Paul Tempst,David M. Sabatini +7 more
TL;DR: It is reported that mTOR forms a stoichiometric complex with raptor, an evolutionarily conserved protein with at least two roles in the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels.
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TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
TL;DR: It is shown that TSC1–TSC2 inhibits the p70 ribosomal protein S6 kinase 1 and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation) and these functions are mediated by inhibition of the mammalian target of rapamycin (mTOR).
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Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.
Dos D. Sarbassov,Siraj M. Ali,Do Hyung Kim,David A. Guertin,Robert R. Latek,Hediye Erdjument-Bromage,Paul Tempst,David M. Sabatini +7 more
TL;DR: It is found that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals.