mTOR: from growth signal integration to cancer, diabetes and ageing
TLDR
Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt.Abstract:
In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.read more
Citations
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Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
TL;DR: In this manuscript, the relevant progress about the role of autophagy in the pathogenesis of ocular diseases is reviewed and pharmacological manipulation of Autophagy may provide an alternative therapeutic target for some Ocular diseases.
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Sirtuins as regulators of metabolism and healthspan
TL;DR: The mammalian sirtuin protein family (comprising SIRT1–SIRT7) has received much attention for its regulatory role, mainly in metabolism and ageing, thereby acting as crucial regulators of the network that controls energy homeostasis and as such determines healthspan.
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The functions and regulation of the PTEN tumour suppressor
TL;DR: The repertoire of PTEN functions has recently been expanded to include phosphatase-independent activities and crucial functions within the nucleus, which will undoubtedly inform the rational design of novel therapies.
Journal ArticleDOI
A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB
Carmine Settembre,Carmine Settembre,Roberto Zoncu,Diego L. Medina,Francesco Vetrini,Francesco Vetrini,Serkan Erdin,SerpilUckac Erdin,SerpilUckac Erdin,Tuong Huynh,Tuong Huynh,Mathieu Ferron,Gerard Karsenty,Michel C. Vellard,Valeria Facchinetti,David M. Sabatini,Andrea Ballabio +16 more
TL;DR: It is shown that the Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 (mTORC1) on the lysOSomal membrane and the Rag GTPase complex is both necessary and sufficient to regulate starvation‐ and stress‐induced nuclear translocation of TFEB.
Journal ArticleDOI
The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation
TL;DR: The Ras-ERK and PI3K-mTOR signaling pathways were originally modeled as linear signaling conduits activated by different stimuli, yet even early experiments hinted that they might intersect to regulate each other and co-regulate downstream functions.
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.
PatentDOI
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
TL;DR: In this paper, the rictor-mTOR complex was used to identify compounds which modulate Akt activity mediated by the Rictor mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activation.
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Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
TL;DR: It is shown that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3, and it is demonstrated that PKB is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC).
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TSC2 mediates cellular energy response to control cell growth and survival.
TL;DR: It is described that TSC2 is regulated by cellular energy levels and plays an essential role in the cellular energy response pathway and its phosphorylation by AMPK protect cells from energy deprivation-induced apoptosis.
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Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor.
TL;DR: The results suggest that the physiologic role of PPAR gamma 2 is to regulate development of the adipose lineage in response to endogenous lipid activators and that this factor may serve to link the process of adipocyte differentiation to systemic lipid metabolism.