ArticleThe Journal of clinical investigation2018
COP1/DET1/ETS axis regulates ERK transcriptome and sensitivity to MAPK inhibitors.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- ctDNA as a Molecular Biomarker in the Phase II Trial of Imatinib plus Binimetinib in Patients with Advanced Gastrointestinal Stromal Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Phase II Trial of Imatinib Plus Binimetinib in Patients With Treatment-Naive Advanced Gastrointestinal Stromal Tumor.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- ETV1 Couples Reciprocal FGF23 and PTH Signaling to RenalResearch square · 2026Article
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- CRISPR knockout screens reveal JUN as the master mediator of resistance to MAPK inhibition in KRAS-mutant pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Deubiquitination of ETV4 by USP7 Promotes NSCLC Tumorigenesis via MAPK7 Activation.Human mutation · 2026Article
- COP1 Deficiency in BRAFCells · 2025Article
- DET1 dynamics underlie cooperative ubiquitination by CRL4Science advances · 2025Article
- Impairment of DET1 causes neurological defects and lethality in mice and humans.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ang-1 and VEGF: central regulators of angiogenesis.Molecular and cellular biochemistry · 2025Review
- Comprehensive analysis of the functional and immunological significance of ETV4 in pan-cancer and its validation in digestive tumors.Frontiers in immunology · 2025Article
- Functional and structural insights into RAS effector proteins.Molecular cell · 2024Review
- Article
- Treatment ofJournal of gastrointestinal oncology · 2024Article
- Functional analysis of recurrent CDC20 promoter variants in human melanoma.Communications biology · 2023Article
- Landscape of enhancer disruption and functional screen in melanoma cells.Genome biology · 2023Article
- Computational prognostic evaluation of Alzheimer's drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches.Scientific reports · 2023Article
- ETV4 mediates dosage-dependent prostate tumor initiation and cooperates with p53 loss to generate prostate cancer.Science advances · 2023Article
- PSMD2 contributes to the progression of esophageal squamous cell carcinoma by repressing autophagy.Cell & bioscience · 2023Article
- Durable responses to alectinib in murine models of EML4-ALK lung cancer requires adaptive immunity.NPJ precision oncology · 2023Article
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
Abstract
Aberrant activation of MAPK signaling leads to the activation of oncogenic transcriptomes. How MAPK signaling is coupled with the transcriptional response in cancer is not fully understood. In 2 MAPK-activated tumor types, gastrointestinal stromal tumor and melanoma, we found that ETV1 and other Pea3-ETS transcription factors are critical nuclear effectors of MAPK signaling that are regulated through protein stability. Expression of stabilized Pea3-ETS factors can partially rescue the MAPK transcriptome and cell viability after MAPK inhibition. To identify the players involved in this process, we performed a pooled genome-wide RNAi screen using a fluorescence-based ETV1 protein stability sensor and identified COP1, DET1, DDB1, UBE3C, PSMD4, and COP9 signalosome members. COP1 or DET1 loss led to decoupling between MAPK signaling and the downstream transcriptional response, where MAPK inhibition failed to destabilize Pea3 factors and fully inhibit the MAPK transcriptome, thus resulting in decreased sensitivity to MAPK pathway inhibitors. We identified multiple COP1 and DET1 mutations in human tumors that were defective in the degradation of Pea3-ETS factors. Two melanoma patients had de novo DET1 mutations arising after vemurafenib treatment. These observations indicate that MAPK signaling-dependent regulation of Pea3-ETS protein stability is a key signaling node in oncogenesis and therapeutic resistance to MAPK pathway inhibition.
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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.