ArticleCell reports2022
Caspase cleavage and nuclear retention of the energy sensor AMPK-α1 during apoptosis.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- AMPK Limits MNNG-Induced Parthanatos by Inhibiting BH3-Only Protein Bim.International journal of molecular sciences · 2025Article
- Depleting chemoresponsive mitochondrial fission mediator DRP1 does not mitigate sarcoma resistance.Life science alliance · 2025Article
- AMPK phosphosite profiling by label-free mass spectrometry reveals a multitude of mTORC1-regulated substrates.npj metabolic health and disease · 2025Article
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- Innovations in radiotherapy for tongue squamous cell carcinoma.Journal of translational medicine · 2024Article
- MitoAMPK inhibits the Warburg effect by MZF1-SIRT6 with glycosis related genes in NSCLC.Journal of cellular and molecular medicine · 2024Article
- Fine-tuning AMPK in physiology and disease using point-mutant mouse models.Disease models & mechanisms · 2024Review
- Ginsenoside Rh2 regulates triple-negative breast cancer proliferation and apoptosis via the IL-6/JAK2/STAT3 pathway.Frontiers in pharmacology · 2024Article
- Hypoxanthine phosphoribosyl transferase 1 metabolizes temozolomide to activate AMPK for driving chemoresistance of glioblastomas.Nature communications · 2023Article
- Critical requirement of SOS1 for tumor development and microenvironment modulation in KRASNature communications · 2023Article
- Article
- New insights into activation and function of the AMPK.Nature reviews. Molecular cell biology · 2023Review
- Cell survival following direct executioner-caspase activation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- AMP-activated protein kinase - a journey from 1 to 100 downstream targets.The Biochemical journal · 2022Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
AMP-activated protein kinase (AMPK) coordinates energy homeostasis during metabolic and energy stress. We report that the catalytic subunit isoform AMPK-α1 (but not α2) is cleaved by caspase-3 at an early stage during induction of apoptosis. AMPK-α1 cleavage occurs following Asp529, generating an ∼58-kDa N-terminal fragment (cl-AMPK-α1) and leading to the precise excision of the nuclear export sequence (NES) from the C-terminal end. This cleavage does not affect (1) the stability of pre-formed heterotrimeric complexes, (2) the ability of cl-AMPK-α1 to become phosphorylated and activated by the upstream kinases LKB1 or CaMKK2, or (3) allosteric activation by AMP or A-769662. Importantly, cl-AMPK-α1 is only detectable in the nucleus, consistent with removal of the NES, and ectopic expression of cleavage-resistant D529A-mutant AMPK-α1 promotes cell death induced by cytotoxic agents. Thus, we have elucidated a non-canonical mechanism of AMPK activation within the nucleus, which protects cells against death induced by DNA damage.
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Registered trials
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.