ArticleProceedings of the National Academy of Sciences of the United States of America2001
Regulation of CD40 function by its isoforms generated through alternative splicing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 137 citations in OpenAlex.
- Soluble CD40 Levels in Rheumatoid Arthritis: Association with Serum Cytokines and Autoantibody Status.Journal of clinical medicine · 2026Article
- Pervasive non-triplet alternative splicing drives functional isoform diversity.Nature communications · 2026Article
- Shared latent genetic liability across fibromyalgia and psychiatric traits: Novel insights from genomic structural equation modeling.PLoS genetics · 2026Article
- Platelets and MMP‑9 contribute to esophageal cancer invasion via CD40‑CD154 interactions.Oncology reports · 2025Article
- An isoform quantitative trait locus in SBNO2 links genetic susceptibility to Crohn's disease with defective antimicrobial activity.Nature communications · 2024Article
- Deciphering the role of alternative splicing in neoplastic diseases for immune-oncological therapies.Frontiers in immunology · 2024Review
- Article
- Catsnap: a user-friendly algorithm for determining the conservation of protein variants reveals extensive parallelisms in the evolution of alternative splicing.The New phytologist · 2023Article
- The RNA-binding protein hnRNP F is required for the germinal center B cell response.Nature communications · 2023Article
- A large-scale plasma proteome Mendelian randomization study identifies novel causal plasma proteins related to primary biliary cholangitis.Frontiers in immunology · 2023Article
- CD40-CD40L in Neurological Disease.International journal of molecular sciences · 2022Review
- Alternative splicing and alternative polyadenylation define tumor immune microenvironment and pharmacogenomic landscape in clear cell renal carcinoma.Molecular therapy. Nucleic acids · 2022Article
- FINER: enhancing the prediction of tissue-specific functions of isoforms by refining isoform interaction networks.NAR genomics and bioinformatics · 2021Article
- Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint.Pharmacology & therapeutics · 2021Review
- Transcriptional splice variants of CD40 and its prognostic value in breast cancer.Turkish journal of biology = Turk biyoloji dergisi · 2020Article
- Association of soluble CD40 levels with -1 C > T CD40 polymorphism and chronic kidney disease in systemic lupus erythematosus.Molecular genetics & genomic medicine · 2019Article
- CD40-targeted peptide proposed for type 1 diabetes therapy lacks relevant binding affinity to its cognate receptor. Reply to Pagni PP, Wolf A, Lo Conte M et al [letter].Diabetologia · 2019Article
- CRISPR/Cas9 Screens Reveal Multiple Layers of B cell CD40 Regulation.Cell reports · 2019Article
- Multiple sclerosis risk variants alter expression of co-stimulatory genes in B cells.Brain : a journal of neurology · 2018Article
- TACI Isoforms Regulate Ligand Binding and Receptor Function.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD40 is a member of the tumor necrosis factor receptor superfamily. The interaction between CD40 and CD40 ligand (CD154) activates NF-kappa B, Jun N-terminal kinase, and Janus kinase/signal transducers and activators of transcription pathways and promotes B cell growth, differentiation, and survival as well as IL-12 production in macrophages and dendritic cells. We demonstrate here the existence of multiple isoforms of CD40 mRNA generated by alternative splicing and show that their expression is regulated differentially in activated macrophages and dendritic cells. Pre-CD40 RNA is spliced preferentially out to signal-transducible CD40 mRNA in the early stage of activation; half of the CD40 mRNA is replaced by the signal-nontransducible CD40 mRNAs in the later stages (24 h). Using IL-12 p40 gene expression as a reporter for CD40 signaling, we show that three of the alternative isoforms can disable signaling through CD40. The major alternative isoform lacks the membrane-associated endodomain and seems to reduce the amount of the signal-transducible form available on the cell surface. It would seem, therefore, that CD40 expression is controlled by posttranscriptional and posttranslational regulation through alternative splicing. Modulation of isoform expression may provide a mechanism by which cells regulate their susceptibility to CD40L signaling.
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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.