ArticleNature communications2022
The deubiquitinase OTUD1 regulates immunoglobulin production and proteasome inhibitor sensitivity in multiple myeloma.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Identification of immune reconstitution and hematopoiesis restoration by scRNA-seq in bone marrow of multiple myeloma patients treated with high-dose melphalan following auto-HSCT.Cancer biology & medicine · 2026Article
- The role of OTUD1-mediated deubiquitination in disease pathogenesis: from molecular mechanisms to clinical translation.Frontiers in immunology · 2026Review
- OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026Review
- Immune infiltration related PRDX4 facilitates the malignant features and drug resistance of breast cancer.Scientific reports · 2025Article
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- OTUD1 Deficiency Alleviates LPS-Induced Acute Lung Injury in Mice by Reducing Inflammatory Response.Inflammation · 2025Article
- TRIM44 facilitates aggressive behaviors in multiple myeloma through promoting ZEB1 deubiquitination.Discover oncology · 2025Article
- Metabolic reprogramming induced by PSMA4 overexpression facilitates bortezomib resistance in multiple myeloma.Annals of hematology · 2025Article
- KEAP1-NRF2 Interaction in Cancer: Competitive Interactors and Their Role in Carcinogenesis.Cancers · 2025Review
- Beyond the marrow: insights from comprehensive next-generation sequencing of extramedullary multiple myeloma tumors.Leukemia · 2024Article
- OTUD1 promotes hypertensive kidney fibrosis and injury by deubiquitinating CDK9 in renal epithelial cells.Acta pharmacologica Sinica · 2024Article
- MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis.Journal of experimental & clinical cancer research : CR · 2024Article
- Factors determining the sensitivity to proteasome inhibitors of multiple myeloma cells.Frontiers in pharmacology · 2024Review
- The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Pleiotropic Roles of a KEAP1-Associated Deubiquitinase, OTUD1.Antioxidants (Basel, Switzerland) · 2023Review
- The pro-tumorigenic cytokine IL-32 has a high turnover in multiple myeloma cells due to proteolysis regulated by oxygen-sensing cysteine dioxygenase and deubiquitinating enzymes.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serum monoclonal immunoglobulin (Ig) is the main diagnostic factor for patients with multiple myeloma (MM), however its prognostic potential remains unclear. On a large MM patient cohort (n = 4146), we observe no correlation between serum Ig levels and patient survival, while amount of intracellular Ig has a strong predictive effect. Focused CRISPR screen, transcriptional and proteomic analysis identify deubiquitinase OTUD1 as a critical mediator of Ig synthesis, proteasome inhibitor sensitivity and tumor burden in MM. Mechanistically, OTUD1 deubiquitinates peroxiredoxin 4 (PRDX4), protecting it from endoplasmic reticulum (ER)-associated degradation. In turn, PRDX4 facilitates Ig production which coincides with the accumulation of unfolded proteins and higher ER stress. The elevated load on proteasome ultimately potentiates myeloma response to proteasome inhibitors providing a window for a rational therapy. Collectively, our findings support the significance of the Ig production machinery as a biomarker and target in the combinatory treatment of MM patients.
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