ArticleEMBO molecular medicine2016
USP9X stabilizes XIAP to regulate mitotic cell death and chemoresistance in aggressive B-cell lymphoma.
Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 65 citations in OpenAlex.
- USP25 augments XIAP-mediated signaling to safeguard intestinal homeostasis.Cell death and differentiation · 2026Article
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- HER2 Heterogeneous Breast Cancer Models Reveal Novel Therapeutic Targets and Subclonal Dynamics during Evolution to Resistance to HER2-Targeted Therapies.Cancer discovery · 2026Article
- Global analysis of cancer cell responses to USP9X inhibition.The EMBO journal · 2026Article
- Mechanisms of chemoresistance in diffuse large B‑cell lymphoma and novel therapeutic strategies (Review).International journal of oncology · 2026Review
- HDAC6 and USP9X Control Glutamine Metabolism by Stabilizing GS to Promote Glioblastoma Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- USP9X integrates TGF-β and hypoxia signalings to promote ovarian cancer chemoresistance via HIF-2α-maintained stemness.Cell death & disease · 2025Article
- Review
- Ubiquitin system mutations in neurological diseases.Trends in biochemical sciences · 2024Review
- USP9X regulates the proliferation, survival, migration and invasion of gastric cancer cells by stabilizing MTH1.BMC gastroenterology · 2024Article
- Review
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Roles of USP9X in cellular functions and tumorigenesis (Review).Oncology letters · 2023Review
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- The Emerging Role of Deubiquitinases in Cell Death.Biomolecules · 2022Review
- USP7 targets XIAP for cancer progression: Establishment of a p53-independent therapeutic avenue for glioma.Oncogene · 2022Article
- Role of the DUB enzyme USP7 in dendritic arborization, neuronal migration, and autistic-like behaviors in mice.iScience · 2022Article
- The role of Ubiquitination in Apoptosis and Necroptosis.Cell death and differentiation · 2022Review
- Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins.International journal of molecular sciences · 2022Review
- USP9X Increased Tumor Angiogenesis in Mantle Cell Lymphoma by Upregulation of CCND1-Mediated SOX11.Mediterranean journal of hematology and infectious diseases · 2022Article
Corrections and comments
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Authors and funding
23 authors at 10 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mitotic spindle assembly checkpoint (SAC) maintains genome stability and marks an important target for antineoplastic therapies. However, it has remained unclear how cells execute cell fate decisions under conditions of SAC-induced mitotic arrest. Here, we identify USP9X as the mitotic deubiquitinase of the X-linked inhibitor of apoptosis protein (XIAP) and demonstrate that deubiquitylation and stabilization of XIAP by USP9X lead to increased resistance toward mitotic spindle poisons. We find that primary human aggressive B-cell lymphoma samples exhibit high USP9X expression that correlate with XIAP overexpression. We show that high USP9X/XIAP expression is associated with shorter event-free survival in patients treated with spindle poison-containing chemotherapy. Accordingly, aggressive B-cell lymphoma lines with USP9X and associated XIAP overexpression exhibit increased chemoresistance, reversed by specific inhibition of either USP9X or XIAP. Moreover, knockdown of USP9X or XIAP significantly delays lymphoma development and increases sensitivity to spindle poisons in a murine Eμ-Myc lymphoma model. Together, we specify the USP9X-XIAP axis as a regulator of the mitotic cell fate decision and propose that USP9X and XIAP are potential prognostic biomarkers and therapeutic targets in aggressive B-cell lymphoma.
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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.