ArticleProceedings of the National Academy of Sciences of the United States of America2013
Myc-induced AMPK-phospho p53 pathway activates Bak to sensitize mitochondrial apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 139 citations in OpenAlex.
- Switching of the c-Myc protein degradation pathway depending on the PP2A-B55α complex levels.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Nucleolus as a cornerstone linking proliferation and metabolism to cellular responses to stress: involvement of transcription factors MYC and p53.Frontiers in molecular biosciences · 2026Review
- Evidence that metformin promotes fibrosis resolutionActa pharmaceutica Sinica. B · 2025Article
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- Metformin and chloroquine enhanced the efficacy of cytarabine in acute lymphoblastic leukemia cell lines: a drug repositioning approach.Scientific reports · 2025Article
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- Transferrin promotes fatty acid oxidation and liver tumor growth through PHD2-mediated PPARα hydroxylation in an iron-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancer.Scientific reports · 2025Article
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- RB1 loss induces quiescent state through downregulation of RAS signaling in mammary epithelial cells.Cancer science · 2024Article
- Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.Metabolites · 2024Review
- AMPK/PGC-1α and p53 modulate VDAC1 expression mediated by reduced ATP level and metabolic oxidative stress in neuronal cells.Acta biochimica et biophysica Sinica · 2024Article
- Targeted Inhibition of Hsp90 in Combination with Metformin Modulates Programmed Cell Death Pathways in A549 Lung Cancer Cells.Applied biochemistry and biotechnology · 2023Article
- BAX as the mediator of C-MYC sensitizes acute lymphoblastic leukemia to TLR9 agonists.Journal of translational medicine · 2023Article
- Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy.Pharmaceutics · 2023Article
- F-ATP synthase inhibitory factor 1 regulates metabolic reprogramming involving its interaction with c-Myc and PGC1α.Frontiers in oncology · 2023Article
- Small-Molecule Gankyrin Inhibition as a Therapeutic Strategy for Breast and Lung Cancer.Journal of medicinal chemistry · 2022Article
- Prohibitin 1 interacts with p53 in the regulation of mitochondrial dynamics and chemoresistance in gynecologic cancers.Journal of ovarian research · 2022Article
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
- Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic transcription factor Myc deregulates the cell cycle and simultaneously reprograms cellular metabolism to meet the biosynthetic and bioenergetic needs of proliferation. Myc also sensitizes cells to mitochondria-dependent apoptosis. Although metabolic reprogramming has been circumstantially connected to vulnerability to apoptosis, the connecting molecular pathways have remained poorly defined. Here, we show that Myc-induced altered glutamine metabolism involves ATP depletion and activation of the energy sensor AMP-activated protein kinase (AMPK), which induces stabilizing phosphorylation of p53 at Ser15. Under influence of Myc, AMPK-stabilized tumor suppressor protein p53 accumulates in the mitochondria and interacts with the protein complex comprised of B-cell lymphoma 2 (Bcl-2) antagonist/killer (BAK) and Bcl2-like 1 (Bcl-xL). Mitochondrial p53 induces conformational activation of proapoptotic Bak without disrupting the Bak-Bcl-xL interaction. Further liberation of Bak specifically from the p53-activated Bak-Bcl-xL complex leads to spontaneous oligomerization of Bak and apoptosis. Thus, Myc-induced metabolic changes are coupled via AMPK and phospho-p53 to the mitochondrial apoptosis effector Bak, demonstrating a cell-intrinsic mechanism to counteract uncontrolled proliferation.
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