ArticleNature cell biology2022
NRF2 mediates melanoma addiction to GCDH by modulating apoptotic signalling.
Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Identification of neoadjuvant chemoradiotherapy resistance-associated proteins in locally advanced rectal cancer: A pilot study.Oncology letters · 2026Article
- A MAFG~MITF complex drives melanoma phenotype switching and progression.Nature communications · 2026Article
- Systematic analysis of the mitophagy scoring system in the prognosis and immunotherapy of HCC patients.Discover oncology · 2026Article
- Piezo1-ATF3-PPP1r15a Axis Transduces Mechanical Stress into Apoptosis in Glioma Under Low-Intensity Focused Ultrasound.Cancers · 2026Article
- Xing-Pi-Qing-Gan decoction alleviates alcoholic liver disease by down-regulatingWorld journal of gastroenterology · 2026Article
- Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.Cell communication and signaling : CCS · 2026Review
- Uncovering Novel lncRNAs Linked to Melanoma Growth and Migration with CRISPR Inhibition Screening.Cancer research communications · 2025Article
- Mendelian Randomization Analysis of Mitochondria-Related Genes and Screening of Prognostic Genes in Colorectal Cancer.Cancer medicine · 2025Article
- Tangeretin regulates oxidative stress in cutaneous melanoma cells via the Nrf2 signaling pathway.Archives of dermatological research · 2025Article
- Identification of ferroptosis-genes associated with pediatric inflammatory bowel disease bioinformatics and machine learning approaches.Frontiers in immunology · 2025Article
- GCDH Acetylation Orchestrates DNA Damage Response and Autophagy via Mitochondrial ROS to Suppress Hepatocellular Carcinoma Progression.Research (Washington, D.C.) · 2025Article
- Mitochondrial Gene Scoring System: Predicting Prognosis and Precision Therapy for TACE Non-Response in Hepatocellular Carcinoma Patients.Journal of Cancer · 2025Article
- Preserving mitochondrial homeostasis protects against drug-induced liver injury via inducing OPTN (optineurin)-dependent Mitophagy.Autophagy · 2024Article
- Applying metabolic control strategies to engineered T cell cancer therapies.Metabolic engineering · 2024Review
- The small MAF transcription factor MAFG co-opts MITF to promote melanoma progression.bioRxiv : the preprint server for biology · 2024Article
- Review
- A glimpse into novel acylations and their emerging role in regulating cancer metastasis.Cellular and molecular life sciences : CMLS · 2024Review
- The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?Antioxidants (Basel, Switzerland) · 2024Review
- CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Tumour dependency on specific metabolic signals has been demonstrated and often guided numerous therapeutic approaches. We identify melanoma addiction to the mitochondrial protein glutaryl-CoA dehydrogenase (GCDH), which functions in lysine metabolism and controls protein glutarylation. GCDH knockdown induced cell death programmes in melanoma cells, an activity blocked by inhibition of the upstream lysine catabolism enzyme DHTKD1. The transcription factor NRF2 mediates GCDH-dependent melanoma cell death programmes. Mechanistically, GCDH knockdown induces NRF2 glutarylation, increasing its stability and DNA binding activity, with a concomitant transcriptional upregulation of ATF4, ATF3, DDIT3 and CHAC1, resulting in cell death. In vivo, inducible inactivation of GCDH effectively inhibited melanoma tumour growth. Correspondingly, reduced GCDH expression correlated with improved survival of patients with melanoma. These findings identify melanoma cell addiction to GCDH, limiting apoptotic signalling by controlling NRF2 glutarylation. Inhibiting the GCDH pathway could thus represent a therapeutic approach to treat melanoma.
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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.