ArticleCancer research2014
E3 ubiquitin ligase HOIP attenuates apoptotic cell death induced by cisplatin.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed, 66 citations in OpenAlex.
- Advancing targeted protein degradation: pLIRTAC's role in glioma and CAR-T cell therapy.Autophagy · 2026Article
- RNF31 induces paclitaxel resistance by sustaining ALYREF cytoplasmic-nuclear shuttling in human triple-negative breast cancer.Clinical and translational medicine · 2025Article
- Therapeutic Chemoresistance in Ovarian Cancer: Emerging Hallmarks, Signaling Mechanisms and Alternative Pathways.Current medicinal chemistry · 2025Review
- Clonal differences underlie variable responses to sequential and prolonged treatment.Cell systems · 2024Article
- Novel players in the development of chemoresistance in ovarian cancer: ovarian cancer stem cells, non-coding RNA and nuclear receptors.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.Cell communication and signaling : CCS · 2023Review
- The mechanism of linear ubiquitination in regulating cell death and correlative diseases.Cell death & disease · 2023Review
- High expression of RNF31 is associated with tumor immune cell infiltration and leads to poor prognosis in liver hepatocellular carcinoma.Scientific reports · 2023Article
- Advances in the Structural and Physiological Functions of SHARPIN.Frontiers in immunology · 2022Review
- HOIP limits anti-tumor immunity by protecting against combined TNF and IFN-gamma-induced apoptosis.EMBO reports · 2021Article
- Linear Ubiquitination Mediates EGFR-Induced NF-κB Pathway and Tumor Development.International journal of molecular sciences · 2021Article
- Review
- Met1-linked ubiquitin signalling in health and disease: inflammation, immunity, cancer, and beyond.Cell death and differentiation · 2021Review
- Review
- The emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- The E3 Ubiquitin Ligase HOIP inhibits Cancer Cell Apoptosis via modulating PTEN stability.Journal of Cancer · 2021Article
- LUBAC-mediated linear ubiquitination: a crucial regulator of immune signaling.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2021Review
- Phenotypic screening using large-scale genomic libraries to identify drug targets for the treatment of cancer.Oncology letters · 2020Review
- The HOIL-1L ligase modulates immune signalling and cell death via monoubiquitination of LUBAC.Nature cell biology · 2020Article
- The Identification of Potential Therapeutic Targets for Cutaneous Squamous Cell Carcinoma.The Journal of investigative dermatology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The genotoxin cisplatin is commonly used in chemotherapy to treat solid tumors, yet our understanding of the mechanism underlying the drug response is limited. In a focused siRNA screen, using an siRNA library targeting genes involved in ubiquitin and ubiquitin-like signaling, we identified the E3 ubiquitin ligase HOIP as a key regulator of cisplatin-induced genotoxicity. HOIP forms, with SHARPIN and HOIL-1L, the linear ubiquitin assembly complex (LUBAC). We show that cells deficient in the HOIP ligase complex exhibit hypersensitivity to cisplatin. This is due to a dramatic increase in caspase-8/caspase-3-mediated apoptosis that is strictly dependent on ATM-, but not ATR-mediated DNA damage checkpoint activation. Moreover, basal and cisplatin-induced activity of the stress response kinase JNK is enhanced in HOIP-depleted cells and, conversely, JNK inhibition can increase cellular resistance to cisplatin and reverse the apoptotic hyperactivation in HOIP-depleted cells. Furthermore, we show that HOIP depletion sensitizes cancer cells, derived from carcinomas of various origins, through an enhanced apoptotic cell death response. We also provide evidence that ovarian cancer cells classified as cisplatin-resistant can regain sensitivity following HOIP downregulation. Cumulatively, our study identifies a HOIP-regulated antiapoptotic signaling pathway, and we envisage HOIP as a potential target for the development of combinatorial chemotherapies to potentiate the efficacy of platinum-based anticancer drugs.
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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.