Cell Biology | Chemical Biology | Published in Nature Chemical Biology, May 14, 2026
University of California San Diego | Shu Chien-Gene Lay Department of Bioengineering
Every cell in your body is running a continuous calculation.
How much food is available? How much energy do we have? Should we grow? Should we divide? Should we break down our own components and recycle them to survive a period of scarcity?
The central machine
mTORC1 is one of the cell’s most important decision-making systems. It senses nutrients, energy, oxygen, and growth signals, then tells the cell whether to grow or conserve resources.
The molecular machine that sits at the centre of this calculation is called mTORC1, short for mechanistic target of rapamycin complex 1. It is one of the most important signaling complexes in the biology of any organism that has cells with nuclei. It integrates information from growth factors, amino acids, oxygen levels, and energy status, and based on that information, it tells the cell what to do next.
For decades, scientists believed they understood where this machine worked: primarily at the lysosome, the cellular compartment that acts as both waste disposal unit and nutrient recycling centre. When nutrients arrive, mTORC1 is recruited to the lysosomal membrane, activated, and begins sending signals throughout the cell: build more proteins, grow, divide, do not break yourself down.
Then, a few years ago, researchers started noticing something that did not fit this tidy picture.
mTORC1 appeared to be active in the nucleus too.
Not just present. Active. Working. But doing what? Nobody could say, because nobody had a way to turn it off in only the nucleus while leaving it running everywhere else. All the tools scientists had for studying mTORC1 worked across the entire cell simultaneously, making it impossible to isolate what the nuclear version specifically contributed.
A team at UC San Diego, led by Professor Jin Zhang, built a new tool to solve that problem. They called it TerminaTOR.
And what they found when they pointed it at the nucleus rewrites how we understand one of the most studied signaling pathways in all of biology.
mTORC1: A Machine Everyone Has Heard About and Almost Nobody Fully Understands
Before explaining what TerminaTOR does, it is worth taking a moment to properly introduce what it targets.
mTORC1 is a complex of multiple proteins, anchored by the mTOR kinase itself, which acts as a sensor and relay station for the cell’s nutritional and growth environment. When conditions are favorable, mTORC1 is active, and it drives anabolic processes: protein synthesis, ribosome biogenesis, lipid synthesis, cell growth, and division. When conditions are unfavorable, when nutrients are scarce or the cell is under stress, mTORC1 activity falls, and the cell switches to autophagy: a controlled self-digestion process that breaks down damaged proteins and organelles and recycles their components for fuel and building materials.
Growth versus recycling
When nutrients are abundant, mTORC1 promotes growth. When nutrients are scarce, mTORC1 activity drops and autophagy begins.
mTORC1 as a nutrient sensor controls numerous cellular functions such as promoting protein synthesis by phosphorylating ribosomal S6 kinase 1 (S6K1) and eIF4E-binding protein 1 (4EBP1) and inhibiting autophagy by phosphorylating the Unc-51-like kinase 1 (ULK1).
It is, in a very literal sense, the cell’s growth and survival switch.
Its importance to medicine is correspondingly enormous. mTORC1 is hyperactivated in a remarkably wide range of cancers: mutations in the pathway that activates mTORC1, including mutations in PTEN, TSC1, TSC2, and RAS, are among the most common oncogenic events. Overactive mTORC1 is also implicated in metabolic diseases including type 2 diabetes, where insulin resistance disrupts normal mTORC1 regulation. A drug called rapamycin, originally discovered as an antifungal compound and named after Rapa Nui, Easter Island, where the bacterium producing it was found, was among the first targeted cancer therapies. Multiple rapamycin analogs, called rapalogs, are used to treat specific cancers. Next-generation mTOR inhibitors are in clinical use and development.
Despite all of this, the full biology of mTORC1 is not understood. Because the standard model, that mTORC1 lives at the lysosome and signals from there, turned out to be incomplete.
The Problem With the Map
In biology, a protein’s location matters enormously. The same protein can do completely different things in different parts of a cell, because the proteins it encounters, the substrates available to it, and the signals it receives are all different depending on where it is.
mTORC1 components and regulators have been reported at numerous locations across the cell, including the nucleus, plasma membrane, mitochondria, and peroxisomes, suggesting that distinct mTORC1 pools could support specialized local functions.
Location matters
A signal at the lysosome may control autophagy. A signal in the nucleus may control gene expression. Global inhibitors cannot separate these jobs.
Nuclear mTORC1 activity, for example, stimulated by growth factors, was detected using a genetically encoded fluorescence resonance energy transfer (FRET)-based mTORC1 activity reporter called TORCAR. This noncanonical nuclear mTORC1 activity is dependent on nuclear Akt activity, which promotes nuclear translocation of Raptor, a defining component of mTORC1, and phosphorylates PRAS40, a negative mTORC1 regulatory protein, to relieve its inhibition of nuclear mTORC1 activity. The functionality of the nuclear pool is still unknown.
Unknown, despite years of knowing it was there. The reason was the tools.
All the drugs and genetic techniques that scientists had for studying mTORC1 worked globally. Rapamycin, one of the most widely used mTOR inhibitors, shuts down mTORC1 everywhere in the cell simultaneously. So does Torin 1, another commonly used inhibitor. Knocking down the genes for key mTORC1 components similarly eliminates the complex from all cellular locations at once.
If you use a tool that affects mTORC1 everywhere and then observe that gene expression changes, you cannot tell whether those changes were driven by nuclear mTORC1, lysosomal mTORC1, mitochondrial mTORC1, or some combination. The question of what nuclear mTORC1 specifically does was trapped behind the absence of a location-specific tool.
The available pharmacological and genetic approaches to mTORC1 have key limitations. ATP-competitive mTOR inhibitors indistinguishably inhibit the kinase activity of both mTORC1 and mTORC2. Rapalogs incompletely block mTORC1 outputs, often only partially dephosphorylating 4EBP1. Bisteric inhibitors more potently inhibit 4EBP1 but still exert global, non-spatially restricted blockade of mTORC1. A selective, genetically encoded mTORC1 inhibitor that can be targeted to defined subcellular locations is still lacking for dissecting the functions of specific mTORC1 pools.
That gap is what TerminaTOR was built to fill.
Building TerminaTOR: Engineering a Molecular Precision Strike
The design of TerminaTOR is an elegant piece of molecular engineering, and it is worth understanding in some detail because the cleverness of the solution is part of the story.
The starting point was a protein called PRAS40, which is an endogenous negative regulator of mTORC1. PRAS40 interacts with mTORC1 through three key structural motifs: the TOR signaling (TOS) motif, a beta-strand, and an alpha-helix. Because of this multisite binding mode, PRAS40 binds to mTORC1 with higher affinity than endogenous mTORC1 substrates such as 4EBP1 and S6K1. This means PRAS40 can competitively block mTORC1 from phosphorylating its normal targets.
The engineering idea
Take the inhibitory part of PRAS40, remove the switches that turn it off, and target it to one precise location inside the cell.
The Zhang lab reasoned that a fragment of PRAS40 retaining all three key binding motifs would act as a competitive inhibitor: it would grab onto mTORC1 tightly enough to prevent it from acting on anything else, effectively freezing the complex.
But there was a complication. PRAS40 itself is regulated by upstream signals. Akt, the kinase immediately upstream of mTORC1 in the growth factor signaling pathway, phosphorylates PRAS40 at specific sites to relieve its inhibition of mTORC1. If the TerminaTOR fragment retained these Akt phosphorylation sites, then when cells received growth factor signals, Akt would simply phosphorylate and neutralize TerminaTOR, defeating the purpose of the tool.
The team solved this by substituting two key regulatory amino acids in the PRAS40 fragment: serine 183 and threonine 246 were changed to alanine, a modification that prevents Akt from phosphorylating these sites. Without these phosphorylation events, TerminaTOR cannot be deactivated by upstream signaling. It is constitutively active as an mTORC1 inhibitor regardless of the cell’s growth factor status.
The best performing fragment, designated 114-245A, inhibited TORCAR responses to a similar extent to full-length PRAS40 expression or Torin 1 treatment. Importantly, when the team used immunoprecipitation to pull down the mCherry-tagged fragment, they detected both mTOR and Raptor, confirming its physical interaction with the mTORC1 complex.
This fragment became TerminaTOR: Targetable and Encodable Repressor to Minimize Activity of mTORC1.
TerminaTOR Versus Existing Drugs: A Meaningful Comparison
Before using TerminaTOR as a discovery tool, the team rigorously characterized how it compares to existing mTOR inhibitors.
On the question of potency: both the small-molecule inhibitors rapamycin and Torin 1 successfully abolished S6K1 phosphorylation, and TerminaTOR achieved similar inhibition. On the critical substrate 4EBP1, rapamycin fell short: it did not fully abolish 4EBP1 phosphorylation, consistent with previous reports that 4EBP1 is a relatively rapamycin-insensitive mTORC1 substrate. TerminaTOR showed better inhibitory effect on 4EBP1 phosphorylation, suggesting the ability to inhibit phosphorylation of a broader range of mTORC1 substrates.
Why TerminaTOR is different
It is genetically encodable, mTORC1-specific, mTORC2-sparing, and can be directed to precise subcellular locations.
On the question of specificity: Torin 1 is an ATP-competitive inhibitor that acts on the mTOR kinase domain and inhibits not only mTORC1 but also mTORC2, a structurally and functionally distinct complex. This is a significant problem when studying mTORC1-specific biology. TerminaTOR did not significantly change PDGF-induced phosphorylation of the mTORC2-specific substrate Akt S473, suggesting that TerminaTOR targets mTORC1 specifically while sparing mTORC2 activity.
On the question of off-target effects: the team examined whether TerminaTOR affected the activity of three other major kinases: Akt, protein kinase A (PKA), and protein kinase C (PKC). In all three cases, TerminaTOR had no detectable effect. Immunoprecipitation-mass spectrometry confirmed that TerminaTOR interacted with mTORC1 but no other protein kinases.
The conclusion: TerminaTOR is a more specific mTORC1 inhibitor than rapamycin, at least as potent as Torin 1 against the full range of mTORC1 substrates, and unlike Torin 1, it spares mTORC2. It is also genetically encodable, meaning it can be fused to targeting sequences and directed to specific locations in the cell.
That last property is what makes it genuinely new.
Lyso-TerminaTOR: Confirming What We Thought We Knew
The first targeted version the team built was Lyso-TerminaTOR: TerminaTOR fused to a sequence derived from LAMP1, a lysosomal membrane protein, which directed the inhibitor specifically to the lysosomal surface.
This version served as a validation experiment. If lysosomal mTORC1 is responsible for regulating autophagy, as the standard model predicts, then inhibiting mTORC1 specifically at the lysosome should induce autophagy. And if the tool is truly location-specific, inhibiting lysosomal mTORC1 should not affect mTORC1 activity at other locations.
The validation result
Blocking lysosomal mTORC1 induced autophagy, confirming the classic model and proving the tool could act locally.
Both predictions were borne out.
Lyso-TerminaTOR significantly inhibited lysosomal mTORC1 activity, as measured by the lysosomal-targeted TORCAR reporter. Critically, it did not inhibit mitochondrial mTORC1 activity when tested simultaneously using a mitochondria-targeted TORCAR.
Lyso-TerminaTOR expression increased autophagy markers to levels comparable to full nutrient starvation, as measured by GFP-tagged LC3 puncta formation, by increased phosphorylation of ATG16L1, and by the tandem autophagy reporter RFP-GFP-LC3. Lyso-TerminaTOR expression significantly increased both autophagosome and autolysosome formation to levels comparable to double starvation, indicating robust induction of autophagic flux.
This confirms the canonical model: lysosomal mTORC1 is the pool responsible for restraining autophagy. It also validated TerminaTOR as a spatially precise tool.
Nuc-TerminaTOR: Going Where No Tool Had Gone Before
With the lysosomal validation complete, the team turned to the main scientific question: what is nuclear mTORC1 actually doing?
Building a nuclear-targeted version of TerminaTOR required solving an additional engineering problem. Simply attaching a nuclear localization sequence (NLS) was not sufficient: even three copies of the NLS left a significant amount of TerminaTOR in the cytoplasm. Because TerminaTOR is a potent mTORC1 inhibitor, even a small cytoplasmic population could confound results by inhibiting cytoplasmic or lysosomal mTORC1.
The nuclear key
Nuc-TerminaTOR was engineered to stay only inside the nucleus, allowing scientists to shut down nuclear mTORC1 without disturbing other mTORC1 pools.
The solution came from examining the PRAS40 sequence itself. PRAS40 contains a nuclear export sequence (NES), a molecular signal that actively pumps proteins out of the nucleus into the cytoplasm. This was part of why TerminaTOR kept leaking out of the nucleus even with added NLS sequences.
The team mutated the two key leucine residues of the NES in TerminaTOR to alanine, disabling its ability to be exported. They then tagged this export-deficient TerminaTOR with histone H2A, a protein that is exclusively nuclear. The result was a TerminaTOR that stayed in the nucleus and stayed only in the nucleus, achieving stringent nuclear localization.
The team named this Nuc-TerminaTOR.
They confirmed its specificity with the same rigor as the lysosomal version. Nuc-TerminaTOR significantly suppressed nuclear mTORC1 activity. It did not affect cytosolic mTORC1 activity. It did not affect lysosomal mTORC1 activity. It did not inhibit phosphorylation of the cytosolic mTORC1 substrate S6K1.
And it did not affect autophagy, confirming that nuclear mTORC1 activity does not have an important role in autophagy inhibition. That role belongs to the lysosomal pool.
Now the real question: what does nuclear mTORC1 do instead?
Nuclear mTORC1 Controls a Specific Program of Gene Transcription
To find out what nuclear mTORC1 specifically does, the team generated NIH3T3 cells stably expressing either Nuc-TerminaTOR or a nuclear-targeted mCherry control under an inducible promoter, stimulated both groups with the growth factor PDGF, and performed RNA sequencing to profile the complete transcriptome of each group.
Critically, they also treated cells with cycloheximide, a protein synthesis inhibitor, to distinguish genes directly regulated at the level of transcription by nuclear mTORC1 from genes whose transcript levels changed because nuclear mTORC1 affected the translation of other regulatory proteins, which then affected transcription. This methodological step isolated the direct transcriptional role of nuclear mTORC1.
The discovery
Nuclear mTORC1 controls a specific gene expression program linked to CCAAT-motif promoters.
The results were clear and specific.
Cells expressing Nuc-TerminaTOR, with nuclear mTORC1 inhibited, showed several hundred differentially expressed genes compared to control cells. A large portion of these overlapped with PDGF-stimulated and rapamycin-sensitive genes, suggesting that growth-factor-induced noncanonical nuclear mTORC1 activity can regulate gene transcription.
The next question was: what do these genes have in common?
The team analyzed the promoter regions of the differentially expressed genes using HOMER, a bioinformatics tool for identifying enriched sequence motifs. The result was striking. Among all the enriched motifs in the promoters of genes regulated by nuclear mTORC1, the CCAAT motif ranked at the top.
CCAAT is a short DNA sequence that appears in the promoter regions of a large fraction of eukaryotic genes. It serves as a binding site for a class of transcription factors including the nuclear factor Y (NF-Y) family and the C/EBP family. These transcription factors, when bound to CCAAT motifs, recruit co-activators that promote gene expression.
Nuclear mTORC1, it turns out, is specifically driving the expression of a subset of genes whose promoters contain CCAAT motifs.
To validate this directly, the team constructed a luciferase reporter gene driven by the CCAAT-containing promoter of a gene called RhoB, one of the differentially expressed CCAAT-motif genes. In cells stimulated with PDGF, expression of Nuc-TerminaTOR significantly reduced luciferase output compared to control cells. When the CCAAT motif was removed from the reporter, PDGF could no longer induce luciferase expression at all, confirming that the CCAAT motif is necessary for the growth-factor-dependent expression of relevant genes.
The Molecular Mechanism: mTORC1, p300, and Histone Acetylation
Finding that nuclear mTORC1 drives CCAAT-motif gene expression raised the next question: how, mechanistically, does it do this?
The CCAAT motif transcription factors NF-Y and C/EBP are known to recruit the histone acetyltransferase p300 to drive gene expression. Histone acetyltransferases like p300 work by adding acetyl groups to the histone proteins around which DNA is wrapped. Acetylated histones adopt a more relaxed configuration that allows the gene transcription machinery to access and read the DNA. p300 is, in this sense, an epigenetic activator: it physically remodels the DNA packaging to make specific genes more accessible.
The pathway
Nuclear mTORC1 activates p300, p300 acetylates histones, and CCAAT-motif genes become transcriptionally active.
Importantly, earlier studies had shown that mTORC1 can phosphorylate p300 and modulate its acetyltransferase activity, although the specific role of nuclear mTORC1 was not defined.
The Zhang lab tested whether Nuc-TerminaTOR, by inhibiting nuclear mTORC1, affected p300 activity. They measured the acetylation of lysine 56 on histone H3 (H3K56), a specific modification carried out by p300. Expression of Nuc-TerminaTOR significantly reduced H3K56 acetylation, similar to treatment with Torin 1. Nuclear mTORC1 inhibition reduces p300 activity, which in turn reduces histone acetylation at the promoters of CCAAT-motif-containing genes, which reduces their transcription.
To confirm this chain of causality, the team treated Nuc-TerminaTOR-expressing cells with CTB, a pharmacological activator of p300. This rescued the expression of CCAAT-motif-containing target genes in cells with nuclear mTORC1 inhibited. Restoring p300 activity downstream of the blocked nuclear mTORC1 signal rescued the transcriptional output.
The pathway is: nuclear mTORC1 activity, stimulated by growth factors, phosphorylates and activates p300, which acetylates histones at CCAAT-motif-containing gene promoters, which enables the transcription of those genes.
When nuclear mTORC1 is shut off by Nuc-TerminaTOR, p300 activity falls, histone acetylation at CCAAT promoters decreases, and the CCAAT-motif gene program is suppressed.
The Cancer Connection
The last piece of the study asks why this matters clinically. CCAAT-motif genes regulate cell growth and proliferation. Nuclear mTORC1 is activated by growth factors. The combination of these two facts suggested a hypothesis: nuclear mTORC1 drives cancer cell proliferation through its control of CCAAT-motif gene expression.
The team tested this in two ways.
First, in NIH3T3 mouse fibroblasts: cells stably expressing Nuc-TerminaTOR showed significantly impaired proliferation compared to control cells at the 48-hour time point.
Second, in CAL33 oral squamous cell carcinoma cells, a human cancer cell line: cells expressing Nuc-TerminaTOR showed reduced cell viability after 72 hours and dramatically impaired colony formation after one week, compared to control cells expressing nuclear mCherry.
Cancer relevance
Nuclear mTORC1 appears to help cancer cells proliferate by controlling a gene-expression program inside the nucleus.
Colony formation assays are a standard measure of oncogenic potential: cells that can form colonies from a single cell have the self-renewal capacity that defines cancer. Nuc-TerminaTOR significantly impaired this capacity specifically in cancer cells.
Nuclear mTORC1, acting through p300 and the CCAAT transcriptional program, promotes cancer cell proliferation. Inhibiting it specifically in the nucleus impairs cancer growth without affecting the cytoplasmic and lysosomal functions of mTORC1 that are needed for normal cellular housekeeping.
This distinction is clinically significant. Current mTOR inhibitors suppress all mTORC1 activity globally, which means they simultaneously block cancer-promoting functions and normal cellular functions including autophagy, protein synthesis regulation, and metabolic sensing. This global suppression is associated with significant side effects and is one reason why mTOR inhibitors have not fulfilled their initial promise as broad cancer treatments.
A strategy that selectively targets nuclear mTORC1, sparing the lysosomal and mitochondrial pools that perform essential metabolic functions, is theoretically a more cancer-specific intervention.
TerminaTOR as a Platform: The Bigger Picture
Beyond the specific findings about nuclear mTORC1 and CCAAT-motif gene regulation, the significance of TerminaTOR as a scientific platform deserves emphasis.
mTORC1 has been reported to be active at the lysosome, plasma membrane, mitochondria, peroxisomes, and now the nucleus. Each of these locations presumably represents a distinct pool with distinct substrates, distinct regulatory inputs, and distinct cellular outputs. Yet the functions of all but the lysosomal pool remain largely unknown, precisely because the tools to study them selectively did not exist.
The bigger breakthrough
TerminaTOR is not just one tool for one discovery. It is a platform for asking what mTORC1 does in different cellular locations.
TerminaTOR changes this. By fusing TerminaTOR to different targeting sequences, researchers can direct it to any subcellular compartment they are interested in, inhibit mTORC1 activity specifically there, and observe what changes. This platform approach could in principle be applied to study mTORC1 at the mitochondria, the plasma membrane, the peroxisome, or any other location where it has been reported to be active.
Each of these investigations could uncover cellular functions of mTORC1 that have been invisible for the same reason the nuclear functions were invisible: the absence of location-specific tools.
The same strategy can also be extended to other kinases and signaling complexes whose activity has been detected at multiple subcellular locations but whose location-specific functions are unknown. Wherever a signaling protein is present in multiple compartments and conventional tools cannot separate the contributions of each pool, a genetically targetable inhibitor based on the same design principles as TerminaTOR could be built and deployed.
TerminaTOR serves as a powerful tool for unraveling spatially regulated functions of mTORC1 across different scales.
What Comes Next
The study was conducted primarily in NIH3T3 mouse fibroblasts and the CAL33 human oral cancer cell line. The next required steps involve expanding to additional cancer types, assessing whether the nuclear mTORC1-p300-CCAAT pathway operates across different tumor types where mTOR is dysregulated, and developing a molecular understanding of which specific CCAAT-motif genes are most critical for the cancer-promoting effects.
The therapeutic translation of this finding is likely years away. TerminaTOR itself is a genetically encoded tool designed for laboratory use. Translating its function into a pharmacological agent, a small molecule or biologics that could selectively inhibit nuclear mTORC1 activity in patients, would require identifying the precise molecular interaction between nuclear mTORC1 and p300 and finding compounds that disrupt it without affecting mTORC1 in other compartments.
Therapeutic caution
This is a powerful discovery tool and a possible future therapeutic direction, but not yet a treatment.
This is a difficult but not unprecedented drug development challenge. The growing field of proximity-targeting drugs, molecules that drive specific protein-protein interactions or disruptions in specific cellular locations, is developing new approaches that could eventually be applied to this problem.
What is established by the current study is the existence and importance of the target: nuclear mTORC1, acting through p300 and histone acetylation at CCAAT-motif gene promoters, promotes cancer cell proliferation through a mechanism that is functionally separable from the canonical lysosomal functions of mTORC1 that regulate autophagy and protein synthesis.
We thought we understood mTORC1. It turns out it was doing something else in the nucleus, something important, something relevant to cancer, and something we could not see until we built a tool precise enough to look.
References and Attributions
Primary Source:
Zhong Y., Sahan A.Z., Shao Z., Zhang Q.Y., Zhou X., Haggett J.G., Koshizuka K., Myers S.A., Gutkind J.S., Zhang J. et al. “Genetically targeted mTORC1 inhibitor reveals transcriptional control by nuclear mTORC1.” Nature Chemical Biology, May 14, 2026; pages 1-12.
DOI: 10.1038/s41589-026-02188-z
URL: https://www.nature.com/articles/s41589-026-02188-z
Lead Corresponding Author:
Professor Jin Zhang, Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
ORCID: 0000-0001-7145-7823
Co-lead Authors:
Yanghao Zhong, UC San Diego
Ayse Z. Sahan, UC San Diego (ORCID: 0000-0003-4661-035X)
Key prior work by the same group:
Zhou X., Zhong Y., Guan K.L., Zhang J. “Location-specific inhibition of Akt reveals regulation of mTORC1 activity in the nucleus.” Nature Communications, 2020; 11: 6088.
DOI: 10.1038/s41467-020-19937-w
Zhou X., Zhang J. et al. “Dynamic visualization of mTORC1 activity in living cells.” Cell Reports, 2015; 10: 1767-1777.
DOI: 10.1016/j.celrep.2015.02.031
Foundational mTORC1 biology:
Saxton R.A., Sabatini D.M. “mTOR signaling in growth, metabolism, and disease.” Cell, 2017; 168: 960-976.
DOI: 10.1016/j.cell.2017.02.004
Sancak Y., Peterson T.R., Shaul Y.D. et al. “Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids.” Cell, 2010; 141: 290-303.
DOI: 10.1016/j.cell.2010.02.024
Kim J., Kundu M., Viollet B., Guan K.L. “AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.” Nature Cell Biology, 2011; 13: 132-141.
DOI: 10.1038/ncb2152
p300 and mTORC1:
Wan W., You Z., Xu Y. et al. “mTORC1 phosphorylates acetyltransferase p300 to regulate autophagy and lipogenesis.” Molecular Cell, 2017; 68: 323-335.
DOI: 10.1016/j.molcel.2017.09.029
Spatial mTORC1:
Fernandes S.A., Sosa Bajo A., Boon R. et al. “Spatial and functional separation of mTORC1 signalling in response to different amino acid sources.” Nature Cell Biology, 2024; 26: 1918-1933.
DOI: 10.1038/s41556-024-01523-7
PRAS40 structural biology:
Yang H., Jiang X., Li B. et al. “Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.” Nature, 2017; 552: 368-373.
DOI: 10.1038/nature25023
Rapamycin and rapalogs:
Lamming D.W., Ye L., Sabatini D.M., Baur J.A. “Rapalogs and mTOR inhibitors as anti-aging therapeutics.” Journal of Clinical Investigation, 2013; 123: 980-989.
DOI: 10.1172/JCI64099
Collaborating Institutions:
University of California San Diego, La Jolla, CA, USA
Salk Institute for Biological Studies, La Jolla, CA, USA
Funding:
The research was supported by grants from the National Institutes of Health.
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