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Upstream and downstream of mTOR
Open accessAbstract
The evolutionarily conserved checkpoint protein kinase, TOR (target of rapamycin), has emerged as a major effector of cell growth and proliferation via the regulation of protein synthesis. Work in the last decade clearly demonstrates that TOR controls protein synthesis through a stunning number of downstream targets. Some of the targets are phosphorylated directly by TOR, but many are phosphorylated indirectly. In this review, we summarize some recent developments in this fast-evolving field. We describe both the upstream components of the signaling pathway(s) that activates mammalian TOR (mTOR) and the downstream targets that affect protein synthesis. We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity.
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“This pathway is an important regulator of cell proliferation and metabolism (Hay and Sonenberg, 2004; Guertin and Sabatini, 2007).”
From Efficient genetic editing of human intestinal organoids using ribonucleoprotein-based CRISPR (2023) · cites this paper as Hay and Sonenberg, 2004
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“In the brain, mTORC1 tightly coordinates different synaptic plasticities -long-term potentiation (LTP) and long-term depression (LTD) -the molecular correlates of learning and memory (2)(3)(4)(5).”
From Analysis of proteins that rapidly change upon mechanistic/mammalian target of rapamycin complex 1 (mTORC1) repression identifies parkinson protein 7 (PARK7) as a novel protein aberrantly expressed in tuberous sclerosis complex (TSC) (2016) · cites this paper as [4]
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Self-citationPhosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling
Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A., & Chen, J. (2001) · Science · doi:10.1126/science.1066015 · Cited by 1,055
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Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies
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“For a more comprehensive picture of mTOR’s function and other pertinent molecular players and pathways, we direct the reader to a more comprehensive review [269].”
BackgroundAkt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity
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Self-citationmTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice
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Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration
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mTOR Kinase Inhibition Causes Feedback-Dependent Biphasic Regulation of AKT Signaling
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Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways
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The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder
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Inflammation and Skeletal Muscle Wasting During Cachexia
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Role of mTOR in physiology and pathology of the nervous system
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Sestrins inhibit mTORC1 kinase activation through the GATOR complex
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Coordination and communication between the p53 and IGF-1–AKT–TOR signal transduction pathways
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mTORC2 controls actin polymerization required for consolidation of long-term memory
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The influence of the intrauterine environment on human placental development
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mTORC1 promotes survival through translational control of Mcl-1
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Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants
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A role for mammalian target of rapamycin in regulating T cell activation versus anergy
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Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks
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ERK1/2 Phosphorylate Raptor to Promote Ras-dependent Activation of mTOR Complex 1 (mTORC1)
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mTORC1 Signaling under Hypoxic Conditions Is Controlled by ATM-Dependent Phosphorylation of HIF-1α
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Mutations in CHMP2B in Lower Motor Neuron Predominant Amyotrophic Lateral Sclerosis (ALS)
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TSC1 Stabilizes TSC2 by Inhibiting the Interaction between TSC2 and the HERC1 Ubiquitin Ligase
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Loss of Tsc1 In Vivo Impairs Hippocampal mGluR-LTD and Increases Excitatory Synaptic Function
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Metadata
- Authors
- Hay, N., & Sonenberg, N.
- Affiliations
- University of Illinois Chicago (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-08-15
- Volume
- 18
- Issue
- 16
- Pages
- 1926-1945
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2129585918
- Cited by
- 4,181
- References
- 13
- Citations by year
- 2026: 40 · 2025: 75 · 2024: 94 · 2023: 144 · 2022: 145 · 2021: 188 · 2020: 208 · 2019: 184 · 2018: 216 · 2017: 219 · 2016: 249 · 2015: 265 · 2014: 280 · 2013: 274 · 2012: 284
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion, cc-by-nc)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- mTOR, TOR signaling, protein synthesis regulation, cell growth, cell proliferation, downstream targets, phosphorylation, cancer, synaptic plasticity
- MeSH terms
- Animals, Cell Division, Energy Metabolism, Growth Substances, Neoplasms, Peptide Initiation Factors, Phosphorylation, Protein Kinases, Transcription, Genetic, Protein Biosynthesis, Ribosomal Protein S6 Kinases, TOR Serine-Threonine Kinases
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