ArticleNature chemical biology2025
ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- Metabolic regulation of calcium homeostasis via SERCA succination.Science advances · 2026Article
- A Novel tRNA Half mt-5'-tiRNA-Tyr Promotes Colorectal Cancer Proliferation via Inducing HARS2 Succinylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Investigation of the effects and underlying mechanisms of adenylate kinase 1 on inosine monophosphate deposition in Beijing-You chickens.Poultry science · 2026Article
- Activating the cGAS-STING pathway in hypoxic microenvironment: blocking ADSL's ER localization.Science China. Life sciences · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- From organelles to therapy: rethinking combined hepatocellular-cholangiocarcinoma.Frontiers in cell and developmental biology · 2026Review
- The impact of asparaginase phenotype-related single nucleotide polymorphisms on prognosis in pediatric B-cell precursor acute lymphoblastic leukemia.European journal of medical research · 2025Article
- Liproxstatin-1 Protects SH-SY5Y Cells by Inhibiting HInternational journal of molecular sciences · 2025Article
- Adenylosuccinate lyase (ADSL) is a pan-cancer prognostic and immune biomarker with distinct roles in hepatocellular carcinoma.Discover oncology · 2025Article
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- Pancreatic Cancer-Targeting Cascade Nanoamplifier Enables Self-Replenishing HPharmaceutics · 2025Article
- ADSL-produced fumarate increases BECN1 dimethylation to promote autophagy and liver tumor growth.Autophagy · 2025Article
Corrections and comments
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Authors and funding
30 authors.
Funding
Abstract
As an enzyme with a critical role in de novo purine synthesis, adenylosuccinate lyase (ADSL) expression is upregulated in various malignancies. However, whether ADSL possesses noncanonical functions that contribute to cancer progression remains poorly understood. Here, we demonstrate that protein kinase R-like endoplasmic reticulum kinase (PERK) activated by lipid deprivation or ER stress phosphorylates ADSL at S140, leading to an enhanced association between ADSL and Beclin1. Beclin1-associated ADSL produces fumarate, which in turn inhibits lysine demethylase 8-mediated Beclin1 demethylation, resulting in enhanced Beclin1 K117me2, subsequent disruption of the binding of BCL-2 to Beclin1 and elevated autophagy. Blocking the ADSL-Beclin1 axis by knock-in mutation or a cell-penetrating peptide inhibits autophagy induced by lipid deprivation and ER stress and blunts liver tumor growth in mice. Additionally, ADSL pS140-upregulated Beclin1 K117me2 levels are positively correlated with autophagy levels in human hepatocellular carcinoma specimens and poor patient prognosis. These findings uncover the function of ADSL in autophagy regulation and liver tumor development.
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39881212What OpenQuestion holds
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.