ArticleNature cell biology2021
TRIM15 and CYLD regulate ERK activation via lysine-63-linked polyubiquitination.
Article in Nature cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases.Molecular neurobiology · 2023Pooled it
- Ubiquitination-dependent regulation of ferroptosis in ischemic heart and brain.Redox biology · 2026Review
- Loss of CYLD on Chromosome 16q Impairs Homologous Recombination and Genomic Stability Through TIRR Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- USP22 deubiquitinates and stabilizes ERK1/2 to promote colorectal cancer progression.Acta pharmacologica Sinica · 2026Article
- ALKBH5/IGF2BP1-mediated mCell biology and toxicology · 2026Article
- The Fas-FasL system: from apoptosis regulator to therapeutic target in autoimmunity, cancer, and transplantation.Immunologic research · 2026Review
- CB2R-mediated GPX4 stabilization: a new avenue for treating cognitive impairment in elderly migraine patients.The journal of headache and pain · 2026Article
- Transcriptomic analysis identifies CXCL12 as a novel candidate gene for litter size in rabbits.Animal bioscience · 2026Article
- Aryl hydrocarbon receptor-dependent lipid droplet accumulation supports redox homeostasis in hypoxia-induced PCa cells.American journal of cancer research · 2026Article
- Targeting TRIM15-mediated Axin1 depolymerization suppresses Wnt signaling and inhibits colorectal cancer growth.Cell death & disease · 2025Article
- Destruction of VISTA by TRIM25 ablation in T cells potentiates cancer immunotherapy.Cell research · 2025Article
- Proteome-wide mendelian randomization identifies FCRL3 and LY9 as potential therapeutic targets for lymphoma.Discover oncology · 2025Article
- TRIM6 ablation reverses ICB resistance in MSS gastric cancer by unleashing cGAS-STING-dependent antitumor immunity.Journal of experimental & clinical cancer research : CR · 2025Article
- Metabolic reprogramming in astrocytes prevents neuronal death through a UCHL1/PFKFB3/H4K8la positive feedback loop.Cell death and differentiation · 2025Article
- The E3 Ubiquitin Ligase ARIH1 Facilitates Colorectal Cancer Progression by Promoting Oxidative Phosphorylation via the Mitochondrial Translocation of K63-Linked Ubiquitinated PHB1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- E3 ligase TRIM22 promotes melanoma proliferation by regulating cell cycle progression through K63-linked ubiquitination of p21.Scientific reports · 2025Article
- Cross-Sectional Study: Associations of A20 and Cezanne with Leukocyte Accumulation in B-Cell Acute Lymphoblastic Leukemia.Medicina (Kaunas, Lithuania) · 2025Article
- Identification of RING E3 pseudoligases in the TRIM protein family.Nature communications · 2025Article
- Cross-ancestry and sex-stratified genome-wide association analyses of amygdala and subnucleus volumes.Nature genetics · 2025Article
- USP13 Facilitates the Proliferation of Hepatocellular Carcinoma Cells by Reducing K48/63-Linked Polyubiquitination and Degradation of PRPF6.Journal of cellular and molecular medicine · 2025Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The extracellular-signal-regulated kinases ERK1 and ERK2 (hereafter ERK1/2) represent the foremost mitogenic pathway in mammalian cells, and their dysregulation drives tumorigenesis and confers therapeutic resistance. ERK1/2 are known to be activated by MAPK/ERK kinase (MEK)-mediated phosphorylation. Here, we show that ERK1/2 are also modified by lysine-63 (K63)-linked polyubiquitin chains. We identify the tripartite motif-containing protein TRIM15 as a ubiquitin ligase and the tumour suppressor CYLD as a deubiquitinase of ERK1/2. TRIM15 and CYLD regulate ERK ubiquitination at defined lysine residues through mutually exclusive interactions as well as opposing activities. K63-linked polyubiquitination enhances ERK interaction with and activation by MEK. Downregulation of TRIM15 inhibits the growth of both drug-responsive and drug-resistant melanomas. Moreover, high TRIM15 expression and low CYLD expression are associated with poor prognosis of patients with melanoma. These findings define a role of K63-linked polyubiquitination in the ERK signalling pathway and suggest a potential target for cancer therapy.
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