ArticleCell death and differentiation2020
Ubiquitin ligase CHIP regulates OTUD3 stability and suppresses tumour metastasis in lung cancer.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 91 citations in OpenAlex.
- HSP90 shields ROC1/RBX1 from proteasomal degradation by CHIP E3 ubiquitin ligase to promote lung adenocarcinoma.Signal transduction and targeted therapy · 2026Article
- GRP78 dysregulation: A proposed molecular mechanism linking the tumor microenvironment to sepsis susceptibility in patients with cancer (Review).International journal of molecular medicine · 2026Review
- Mechanistic investigation of TRIB3-mediated growth, metastasis and ferroptosis in renal cell carcinoma.Human cell · 2026Article
- Dual Targeting of Mutant p53 and SNRPD2 via Engineered Exosomes Modulates Alternative Splicing to Suppress Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- OTU deubiquitinases as immune-circuit editors: from human immunopathology to therapeutic prioritization.Frontiers in immunology · 2026Review
- The dual role of OTUD3 in cancer: mechanisms and therapeutic implications.Cancer cell international · 2025Review
- The STUB1-TPIT axis regulates the secretion of adrenocorticotrophic hormone in cushing disease.Journal of translational medicine · 2025Article
- Phosphorylation enhanced OTUD3 deubiquitination ARID3A promotes the progress of cholangiocarcinoma.Oncogene · 2025Article
- GRP78 as a potential therapeutic target in cancer treatment: an updated review of its role in chemoradiotherapy resistance of cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- Deubiquitinating Enzyme OTUDs: Focus on Cancers and Antiviral Response.Oncology research · 2025Review
- WWP1 targeting PTEN for polyubiquitination to promote bone metastasis of luminal breast cancer.Scientific reports · 2024Article
- Review
- CHIP drives proteasomal degradation of NUR77 to alleviate oxidative stress and intrinsic apoptosis in cisplatin-induced nephropathy.Communications biology · 2024Article
- The deubiquitinase OTUD3 stabilizes IRP2 expression to reduce hippocampal neuron ferroptosis via the p53/PTGS2 pathway to ameliorate cerebral ischemia-reperfusion injury.European journal of medical research · 2024Article
- CHIP ameliorates nonalcoholic fatty liver disease via promoting K63- and K27-linked STX17 ubiquitination to facilitate autophagosome-lysosome fusion.Nature communications · 2024Article
- Research progress in deubiquitinase OTUD3.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Review
- Rupatadine-inhibited OTUD3 promotes DLBCL progression and immune evasion through deubiquitinating MYL12A and PD-L1.Cell death & disease · 2024Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian tumour domain-containing protein 3 (OTUD3), a key OTU (ovarian tumour protease) family deubiquitylase, plays context-dependent roles in cancers. It suppresses tumorigenesis in breast, colon, liver and cervical cancer through stabilizing PTEN (phosphatase and tension homologue deleted on chromosome 10) while promotes lung tumorigenesis through stabilizing GRP78 (The glucose-regulated protein 78 kDa). The regulation especially post-translational modification of OTUD3 remains unclear. Here, we report that the carboxyl terminus of Hsc70-interacting protein (CHIP) is a ubiquitin ligase for OTUD3. CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation. Knockdown of CHIP stabilizes OTUD3 which leads to elevated GRP78 levels in lung cancer cells. CHIP-knockdown lung cancer cells exhibit increased invasion in OTUD3 and GRP78 dependent manner. Further study demonstrates that CHIP-knockdown lung cancer cells are more prone to metastasize to mice lung when injected intravenously or subcutaneously. Moreover, the expression of CHIP is low in human lung cancer tissues and inversely correlates with OTUD3 expression and GRP78 expression. Furthermore, we identified CHIP mutations in human lung cancers, which reduce CHIP catalytic activity. These findings demonstrate that CHIP is a negative regulator of OTUD3 and CHIP suppresses lung cancer metastasis through inhibiting OTUD3-GRP78 signaling axis.
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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.