ArticleOncotarget2014
The cylindromatosis gene product, CYLD, interacts with MIB2 to regulate notch signalling.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- The deubiquitinase activity of CYLD is required for B cell differentiation.Cell death & disease · 2026Article
- Cyld restrains the hyperactivation of synovial fibroblasts in inflammatory arthritis by regulating the TAK1/IKK2 signaling axis.Cell death & disease · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Mind bomb 2 limits inflammatory dermatitis inPNAS nexus · 2024Article
- Genotoxicity-Stimulated and CYLD-Driven Malignant Transformation.Cancer management and research · 2022Article
- Ubiquitination and Deubiquitination in Oral Disease.International journal of molecular sciences · 2021Review
- Genetic Testing in CYLD Cutaneous Syndrome: An Update.The application of clinical genetics · 2021Review
- Review
- CYLD Promotes Apoptosis of Nasopharyngeal Carcinoma Cells by Regulating NDRG1.Cancer management and research · 2020Article
- Loss of Tumor Suppressor CYLD Expression Triggers Cisplatin Resistance in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2019Article
- The E3 ubiquitin ligase MIB2 enhances inflammation by degrading the deubiquitinating enzyme CYLD.The Journal of biological chemistry · 2019Article
- Ectopic expression of E3 ubiquitin-protein ligase 2 in glioma and enhances resistance to apoptosis through activating nuclear factor κ-light-chain-enhancer of B cells.Oncology letters · 2018Article
- Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential.Journal of hematology & oncology · 2018Review
- Loss of CYLD expression unleashes Wnt signaling in multiple myeloma and is associated with aggressive disease.Oncogene · 2017Article
- The role of deubiquitinases in breast cancer.Cancer metastasis reviews · 2016Review
- Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer.Nature medicine · 2016Article
- CYLD Promotes TNF-Mediators of inflammation · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
CYLD, an ubiquitin hydrolase, has an expanding repertoire of regulatory roles in cell signalling and is dysregulated in a number of cancers. To dissect CYLD function we used a proteomics approach to identify CYLD interacting proteins and identified MIB2, an ubiquitin ligase enzyme involved in Notch signalling, as a protein which interacts with CYLD. Coexpression of CYLD and MIB2 resulted in stabilisation of MIB2 protein levels and was associated with reduced levels of JAG2, a ligand implicated in Notch signalling. Conversely, gene silencing of CYLD using siRNA, resulted in increased JAG2 expression and upregulation of Notch signalling. We investigated Notch pathway activity in skin tumours from patients with germline mutations in CYLD and found that JAG2 protein levels and Notch target genes were upregulated. In particular, RUNX1 was overexpressed in CYLD defective tumour cells. Finally, primary cell cultures of CYLD defective tumours demonstrated reduced viability when exposed to γ-secretase inhibitors that pharmacologically target Notch signalling. Taken together these data indicate an oncogenic dependency on Notch signalling and suggest potential novel therapeutic approaches for patients with CYLD defective tumours.
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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.