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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mTORC1 is an important regulator of cell proliferation and metabolism.
“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
The Abstract and the section on mTOR translational control, cell growth, and proliferation describe mTOR as a regulator of cell proliferation. The sections on upstream regulators and control by energy metabolism chiefly describe nutrients and cellular energy regulating mTOR, rather than establishing that mTORC1 regulates metabolism. Our copy therefore supports the proliferation part but not the metabolism part as stated. (LLM, conf=0.83)
Experimental — accuracy not yet measuredmTORC1 tightly coordinates LTP and LTD, the molecular correlates of learning and memory.
“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]
The section “mTOR function in synaptic plasticity, memory, and learning” (page unavailable) identifies LTP as a model of plasticity underlying learning and reports that rapamycin inhibits late LTP. It does not establish that mTORC1 tightly coordinates both LTP and LTD; the supplied passages and searches do not address LTD. (LLM, conf=0.88)
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- 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
- 9
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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