ArticleScientific reports2018
Dynamic modelling of the mTOR signalling network reveals complex emergent behaviours conferred by DEPTOR.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Metabolic Overdrive in Elite Sport: A Systems Model of AMPK-mTOR Oscillation, NADInternational journal of molecular sciences · 2026Review
- Basal State Calibration of a Chemical Reaction Network Model for Autophagy.International journal of molecular sciences · 2024Article
- Multi-Dimensional Analysis of Biochemical Network Dynamics Using pyDYVIPAC.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The mixed blessing of AMPK signaling in Cancer treatments.BMC cancer · 2022Article
- The crosstalk between MYC and mTORC1 during osteoclastogenesis.Frontiers in cell and developmental biology · 2022Article
- Roles of mTOR in thoracic aortopathy understood by complex intracellular signaling interactions.PLoS computational biology · 2021Article
- Dynamic modelling of the PI3K/MTOR signalling network uncovers biphasic dependence of mTORC1 activity on the mTORC2 subunit SIN1.PLoS computational biology · 2021Article
- Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network.International journal of molecular sciences · 2021Review
- The New Omics Era into Systems Approaches: What Is the Importance of Separation Techniques?Advances in experimental medicine and biology · 2021Article
- Article
- Regulation of cellular anabolism by mTOR: or how I learned to stop worrying and love translation.Sports medicine and health science · 2020Review
- mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex.eLife · 2020Article
- TopoFilter: a MATLAB package for mechanistic model identification in systems biology.BMC bioinformatics · 2020Article
- LC3/GABARAPs drive ubiquitin-independent recruitment of Optineurin and NDP52 to amplify mitophagy.Nature communications · 2019Article
- Review
- Network rewiring, adaptive resistance and combating strategies in breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- The Lysosome Signaling Platform: Adapting With the Times.Frontiers in cell and developmental biology · 2019Review
- DEPTOR at the Nexus of Cancer, Metabolism, and Immunity.Physiological reviews · 2018Review
- Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanistic Target of Rapamycin (mTOR) signalling network is an evolutionarily conserved network that controls key cellular processes, including cell growth and metabolism. Consisting of the major kinase complexes mTOR Complex 1 and 2 (mTORC1/2), the mTOR network harbours complex interactions and feedback loops. The DEP domain-containing mTOR-interacting protein (DEPTOR) was recently identified as an endogenous inhibitor of both mTORC1 and 2 through direct interactions, and is in turn degraded by mTORC1/2, adding an extra layer of complexity to the mTOR network. Yet, the dynamic properties of the DEPTOR-mTOR network and the roles of DEPTOR in coordinating mTORC1/2 activation dynamics have not been characterised. Using computational modelling, systems analysis and dynamic simulations we show that DEPTOR confers remarkably rich and complex dynamic behaviours to mTOR signalling, including abrupt, bistable switches, oscillations and co-existing bistable/oscillatory responses. Transitions between these distinct modes of behaviour are enabled by modulating DEPTOR expression alone. We characterise the governing conditions for the observed dynamics by elucidating the network in its vast multi-dimensional parameter space, and develop strategies to identify core network design motifs underlying these dynamics. Our findings provide new systems-level insights into the complexity of mTOR signalling contributed by DEPTOR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.