ArticleBlood2021
MYD88 L265P elicits mutation-specific ubiquitination to drive NF-κB activation and lymphomagenesis.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Genetically driven immune microenvironment states associate with therapeutic responses in MYD88 mutant lymphomas.Molecular cancer · 2026Article
- Rab43 mitigates the inflammatory response in acute lung injury via MyD88 ubiquitination.Scientific reports · 2026Article
- Gut-heart axis disruption and LPS translocation: driving atrial fibrillation through inflammatory storm and fibrotic mechanisms.Frontiers in endocrinology · 2026Review
- The enigma of the RING-UIM E3 ligases: its transformative impact on cancer research.Journal of translational medicine · 2025Review
- USP13 mediates resistance to Ibrutinib in diffuse large B-cell lymphoma via augmenting FHL1 stabilization.American journal of cancer research · 2025Article
- RNF138 regulates skeletal muscle differentiation via the Wnt/β-catenin signaling pathway.Theranostics · 2025Article
- MiR-525-5p modulates cell proliferation, cell cycle, and apoptosis in Burkitt's lymphoma by targeting MyD88 and regulating the NF-κB signaling pathway.Annals of hematology · 2024Article
- Article
- Inhibition of NLRP3 inflammasome activation by A20 through modulation of NEK7.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Exploring the molecular mechanisms between lymphoma and myelofibrosis.American journal of translational research · 2024Review
- USP3 plays a critical role in the induction of innate immune tolerance.EMBO reports · 2023Article
- RNF138 Downregulates Antiviral Innate Immunity by Inhibiting IRF3 Activation.International journal of molecular sciences · 2023Article
- Article
- Transcriptome Analysis of Diffuse Large B-Cell Lymphoma Cells Inducibly Expressing MyD88 L265P Mutation Identifies Upregulated CD44, LGALS3, NFKBIZ, and BATF as Downstream Targets of Oncogenic NF-κB Signaling.International journal of molecular sciences · 2023Article
- PD-L1 translocation to the plasma membrane enables tumor immune evasion through MIB2 ubiquitination.The Journal of clinical investigation · 2023Article
- NF-kB's contribution to B cell fate decisions.Frontiers in immunology · 2023Review
- MiR-525-5p inhibits diffuse large B cell lymphoma progression via the Myd88/NF-κB signaling pathway.PeerJ · 2023Article
- Role of K63-linked ubiquitination in cancer.Cell death discovery · 2022Review
- Expanding anti-CD38 immunotherapy for lymphoid malignancies.Journal of experimental & clinical cancer research : CR · 2022Article
- RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy.Signal transduction and targeted therapy · 2022Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Myeloid differentiation primary response protein 88 (MYD88) is a critical universal adapter that transduces signaling from Toll-like and interleukin receptors to downstream nuclear factor-κB (NF-κB). MYD88L265P (leucine changed to proline at position 265) is a gain-of-function mutation that occurs frequently in B-cell malignancies such as Waldenstrom macroglobulinemia. In this study, E3 ligase RING finger protein family 138 (RNF138) catalyzed K63-linked nonproteolytic polyubiquitination of MYD88L265P, resulting in enhanced recruitment of interleukin-1 receptor-associated kinases and elevated NF-κB activation. However, RNF138 had little effect on wild-type MYD88 (MYD88WT). With either RNF138 knockdown or mutation on MYD88 ubiquitination sites, MYD88L265P did not constitutively activate NF-κB. A20, a negative regulator of NF-κB signaling, mediated K48-linked polyubiquitination of RNF138 for proteasomal degradation. Depletion of A20 further augmented MYD88L265P-mediated NF-κB activation and lymphoma growth. Furthermore, A20 expression correlated negatively with RNF138 expression and NF-κB activation in lymphomas with MYD88L265P and in those without. Strikingly, RNF138 expression correlated positively with NF-κB activation in lymphomas with MYD88L265P, but not in those without it. Our study revealed a novel mutation-specific biochemical reaction that drives B-cell oncogenesis, providing a therapeutic opportunity for targeting oncogenic MYD88L265P, while sparing MYD88WT, which is critical to innate immunity.
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