ArticleThe Journal of biological chemistry2015
AMP-activated Protein Kinase (AMPK) Control of mTORC1 Is p53- and TSC2-independent in Pemetrexed-treated Carcinoma Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review.Cells · 2021Pooled it
- Acute amyloid-β exposure disrupts insulin signaling in hCMEC/D3 blood-brain barrier endothelial cells.Fluids and barriers of the CNS · 2026Article
- Article
- Modulating Th17/Treg Balance in Alzheimer's Disease: Therapeutic Insights from Natural Compounds and Immunometabolism.Brain sciences · 2026Review
- Transcriptional control of PPP2CB by YAP1 and TEAD1 mediates AMPK inhibition and mTORC1 activation in vascular smooth muscle cells.iScience · 2026Article
- Acute amyloid-β exposure disrupts insulin signaling in blood-brain barrier endothelial cell culture models.Research square · 2026Article
- The mitochondrial logic of inflammaging: how energy imbalance drives fibroblast SASP and tissue-specific aging.Frontiers in immunology · 2026Review
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- The Paradox of NET Involvement in the Pathogenesis of Inflammatory Bowel Disease.Inflammatory bowel diseases · 2026Review
- Mitophagy in skeletal muscle: Impact of ageing, exercise and disuse.Experimental physiology · 2025Review
- Glycation-lowering compounds inhibit ghrelin signaling to reduce food intake, lower insulin resistance, and extend lifespan.Cell reports · 2025Article
- Exploring the effects of ROS on PI3K/AKT/mTOR signalling in pediatric low-grade glioma and therapeutic strategies.Molecular biology reports · 2025Review
- The metformin administration on pancreatic tissue damage in metastatic rat prostate cancer and STZ induced diabetes model.Journal of molecular histology · 2025Article
- Progressive Alcohol-Related Brain Atrophy and White Matter Pathology Are Linked to Long-Term Inhibitory Effects on mTOR Signaling.Biomolecules · 2025Article
- Review
- AMPK-mTOR pathway modulates glycolysis reprogramming in unexplained recurrent spontaneous abortion.BMC pregnancy and childbirth · 2024Article
- Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma.British journal of cancer · 2024Article
- Rottlerin Enhances the Autophagic Degradation of Phosphorylated Tau in Neuronal Cells.Molecular neurobiology · 2024Article
- Redistribution of SOD3 expression due to R213G polymorphism affects pulmonary interstitial macrophage reprogramming in response to hypoxia.Physiological genomics · 2024Article
- Beyond self‑eating: Emerging autophagy‑independent functions for the autophagy molecules in cancer (Review).International journal of oncology · 2024Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The key sensor of energy status in mammalian cells, AMP-activated protein kinase (AMPK), can also be activated by the AMP analog aminoimidazolecarboxamide nucleoside monophosphate (ZMP) generated directly from aminoimidazolecarboxamide ribonucleoside (AICAR) or from inhibition of purine synthesis by the antifolate pemetrexed (PTX), a drug used extensively in the treatment of lung cancers. Despite this common mechanism, signaling downstream of AMPK activated by PTX or AICAR differed. AICAR-activated AMPK inhibited mTORC1 both directly by phosphorylation of the mTORC1 subunit Raptor and indirectly by phosphorylation of the regulator TSC2. In contrast, PTX-activated AMPK inhibited mTORC1 solely through Raptor phosphorylation. This dichotomy was due to p53 function. Transcription of p53 target genes, including TSC2, was activated by AICAR but not by PTX. Although both PTX and AICAR stabilized p53, only AICAR activated Chk2 phosphorylation, stimulating p53-dependent transcription. However, Raptor phosphorylation by AMPK was independent of p53 and was sufficient, after PTX treatment, to inhibit mTORC1. We concluded that PTX effects on mTORC1 were independent of TSC2 and p53 and that the activation of a p53 transcriptional response by AICAR was due to an activation of Chk2 that was not elicited by PTX.
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