ArticleCell2015
Degradation of AMPK by a cancer-specific ubiquitin ligase.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 236 papers, 4 of them syntheses that pooled it.
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Who cites it
236 citing papers in PubMed, 4 syntheses or guidelines pooled it, 409 citations in OpenAlex.
- Preventive and Therapeutic effects of Metformin in Cancer: A Meta- Analysis of RCT and Cohort Studies.Current cancer drug targets · 2026Pooled it
- Phytochemicals regulate cancer metabolism through modulation of the AMPK/PGC-1α signaling pathway.BMC cancer · 2024Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Prognostic Value of Melanoma-Associated Antigen-A (MAGE-A) Gene Expression in Various Human Cancers: A Systematic Review and Meta-analysis of 7428 Patients and 44 Studies.Molecular diagnosis & therapy · 2020Pooled it
- Intratumoral microbiota promote pancreatic cancer progression via NaAc-mediated activation of the GPR43/AMPK/HADH pathway.Journal of translational medicine · 2026Article
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Article
- Epithelial-to-mesenchymal transition as a central driver of tumor cell plasticity.Nature cancer · 2026Review
- α-Ketoglutarate dictates AMPK protein synthesis for energy sensing in human cancers.Nature chemical biology · 2026Article
- Cross-Species Upregulation ofCurrent issues in molecular biology · 2026Article
- Melanoma antigen genes A1 and A3 as predictors of treatment response and survival in HCV-associated hepatocellular carcinoma: a prospective study.BMC gastroenterology · 2026Article
- Endothelial KSR2 regulated by genetic variation protects against atherosclerosis through AMPKα1 stabilization.Theranostics · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma.Nature communications · 2025Article
- An SNP-dependent cancer-testis antigenic epitope serves as a promising immunotherapeutic target for cancer.Oncoimmunology · 2025Article
- Targeting the MAGED2-TRIM28-FLNC axis overcomes chemoresistance in TNBC via EMT suppression.Cell communication and signaling : CCS · 2025Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- Cytoplasmic translocation of tripartite motif-containing 28 is critical for PRRSV-induced autophagy through promoting Vps34-Beclin1 complex formation.Journal of virology · 2025Article
- Divergent roles of DNA methylation, TRIM28, and p53 surveillance in human embryonic and trophoblast stem cells.bioRxiv : the preprint server for biology · 2025Article
- Reciprocal stabilization of CtBP and TRIM28 represses autophagy to promote metastasis.Nature structural & molecular biology · 2025Article
176 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
AMP-activated protein kinase (AMPK) is a master sensor and regulator of cellular energy status. Upon metabolic stress, AMPK suppresses anabolic and promotes catabolic processes to regain energy homeostasis. Cancer cells can occasionally suppress the growth-restrictive AMPK pathway by mutation of an upstream regulatory kinase. Here, we describe a widespread mechanism to suppress AMPK through its ubiquitination and degradation by the cancer-specific MAGE-A3/6-TRIM28 ubiquitin ligase. MAGE-A3 and MAGE-A6 are highly similar proteins normally expressed only in the male germline but frequently re-activated in human cancers. MAGE-A3/6 are necessary for cancer cell viability and are sufficient to drive tumorigenic properties of non-cancerous cells. Screening for targets of MAGE-A3/6-TRIM28 revealed that it ubiquitinates and degrades AMPKα1. This leads to inhibition of autophagy, activation of mTOR signaling, and hypersensitization to AMPK agonists, such as metformin. These findings elucidate a germline mechanism commonly hijacked in cancer to suppress AMPK.
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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.