ArticleNature cell biology2024
p300 nucleocytoplasmic shuttling underlies mTORC1 hyperactivation in Hutchinson-Gilford progeria syndrome.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- Progerin Hinders Autophagy Flux at Its Final Stages in Hutchinson-Gilford Progeria Syndrome Cells, Preventing Its Own Autophagic Degradation.Aging cell · 2026Article
- Review
- Lactylation enzymes in cancer: Mechanisms and novel therapeutic approaches (Review).Oncology letters · 2026Review
- Genetically targeted mTORC1 inhibitor reveals transcriptional control by nuclear mTORC1.Nature chemical biology · 2026Article
- Ep300-mediated acetylation plasticity in the acetyl-CoA metabolic network drives the protective role of intensive lifestyle intervention in visceral white adipose tissue.Cell communication and signaling : CCS · 2026Article
- Aerobic exercise facilitates p300 nuclear translocation via ADRB2-AMPKα signaling, leading to enhanced histone acetylation and mitigation of cognitive decline in APP/PS1 mice.Alzheimer's research & therapy · 2026Article
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- Resetting the epigenetic clock: cellular senescence and regenerative strategies in intervertebral disc degeneration.Frontiers in aging · 2026Review
- Article
- Research progress on protein lactylation in female reproductive disease: molecular mechanisms, functions, and therapeutic implications.Frontiers in pharmacology · 2026Review
- Targeting the lactylation of ENO1 alleviates endothelial dysfunction in sepsis.Clinical and translational medicine · 2026Article
- The Roles of Lactate and Lactylation in Diseases Related to Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- Cardiac-specific overexpression of PRMT5 exacerbates pressure overload-induced hypertrophy and heart failure.Journal of biomedical science · 2025Article
- Using RNA therapeutics to promote healthy aging.Nature aging · 2025Review
- Targeting CRM1 for Progeria Syndrome Therapy.Aging cell · 2025Article
- PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation-mediated gene expression.Protein & cell · 2025Article
- New developments in AMPK and mTORC1 cross-talk.Essays in biochemistry · 2024Review
- The endolysosomal system in conventional and unconventional protein secretion.The Journal of cell biology · 2024Review
- Gerogenes and gerosuppression: the pillars of precision geromedicine.Cell research · 2024Article
Corrections and comments
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- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth, metabolism and autophagy. Multiple pathways modulate mTORC1 in response to nutrients. Here we describe that nucleus-cytoplasmic shuttling of p300/EP300 regulates mTORC1 activity in response to amino acid or glucose levels. Depletion of these nutrients causes cytoplasm-to-nucleus relocalization of p300 that decreases acetylation of the mTORC1 component raptor, thereby reducing mTORC1 activity and activating autophagy. This is mediated by AMP-activated protein kinase-dependent phosphorylation of p300 at serine 89. Nutrient addition to starved cells results in protein phosphatase 2A-dependent dephosphorylation of nuclear p300, enabling its CRM1-dependent export to the cytoplasm to mediate mTORC1 reactivation. p300 shuttling regulates mTORC1 in most cell types and occurs in response to altered nutrients in diverse mouse tissues. Interestingly, p300 cytoplasm-nucleus shuttling is altered in cells from patients with Hutchinson-Gilford progeria syndrome. p300 mislocalization by the disease-causing protein, progerin, activates mTORC1 and inhibits autophagy, phenotypes that are normalized by modulating p300 shuttling. These results reveal how nutrients regulate mTORC1, a cytoplasmic complex, by shuttling its positive regulator p300 in and out of the nucleus, and how this pathway is misregulated in Hutchinson-Gilford progeria syndrome, causing mTORC1 hyperactivation and defective autophagy.
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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.