ArticleProceedings of the National Academy of Sciences of the United States of America2023
FBXO11 constitutes a major negative regulator of MHC class II through ubiquitin-dependent proteasomal degradation of CIITA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 22 citations in OpenAlex.
- The effect of cohesin mutations on HLA-class II expression in the myeloid leukemia of Down syndrome.Leukemia · 2026Article
- Protein Posttranslational Modifications in Immunity: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Pleiotropic Roles of FBXO11 in Tumorigenesis: Implications for Targeted Therapy.Cancer science · 2026Review
- CIITA/PRMT5 promote CD4BMC medicine · 2026Article
- Histone methyltransferase DOT1L differentially affects the development of dendritic cell subsets.Life science alliance · 2026Article
- Class II Major Histocompatibility Complex Transactivator (CIITA): A Master MHC-II Regulator Impacting Cancer and Beyond.Journal of immunotherapy and precision oncology · 2026Review
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- FBXO11 and FBXO32 are associated with TRAF3-TBK1-IRF3 signaling components in chronic hepatitis B: evidence from clinical samples and preliminary mechanistic studies.American journal of translational research · 2026Article
- Tumoral RCOR2 promotes tumor development through dual epigenetic regulation of tumor plasticity and immunogenicity.The Journal of clinical investigation · 2025Article
- Regulatory polymorphisms ofJournal for immunotherapy of cancer · 2025Article
- Current landscape of the immunoproteasome: implications for disease and therapy.Cell death discovery · 2025Review
- Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency.HGG advances · 2025Article
- The miR-155-5p/Translational cancer research · 2025Article
- An epigenetic pathway regulates MHC-II expression and function in B cell lymphoma models.The Journal of clinical investigation · 2025Article
- F-box proteins at the crossroads of ubiquitination and tumor immunity: regulatory networks and immunotherapy strategies.Frontiers in immunology · 2025Review
- Beyond gluten: the multifaceted regulation of MHC class II in celiac disease pathogenesis.Gastroenterology and hepatology from bed to bench · 2025Review
- Main Genes Linked to the Immune Microenvironment in High-Grade Serous Ovarian Cancer.Advanced biomedical research · 2025Article
- Protein ubiquitination in ovarian cancer immunotherapy: The progress and therapeutic strategy.Genes & diseases · 2024Review
- FBXO11 Mediates Ubiquitination of ZEB1 and Modulates Epithelial-to-Mesenchymal Transition in Lung Cancer Cells.Cancers · 2024Article
- In vivo CRISPR screens identifyProceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major histocompatibility complex (MHC) class I and II molecules play critical roles in the activation and regulation of adaptive immunity through antigen presentation to CD8+ and CD4+ T cells, respectively. Strict regulation of MHC expression is critical for proper immune responses. CIITA (MHC class II transactivator), an NLR (nucleotide-binding domain, leucine-rich-repeat containing) protein, is a master regulator of MHC class II (MHC-II) gene transcription. Although it has been known that CIITA activity is regulated at the transcriptional and protein levels, the mechanism to determine CIITA protein level has not been elucidated. Here, we show that FBXO11 is a bona fide E3 ligase of CIITA and regulates CIITA protein level through ubiquitination-mediated degradation. A nonbiased proteomic approach for CIITA-binding protein identified FBXO11, a member of the Skp1-Cullin-1-F-box E3 ligase complex, as a binding partner of CIITA but not MHC class I transactivator, NLRC5. The cycloheximide chase assay showed that the half-life of CIITA is mainly regulated by FBXO11 via the ubiquitin-proteasome system. The expression of FBXO11 led to the reduced MHC-II at the promoter activity level, transcriptional level, and surface expression level through downregulation of CIITA. Moreover, human and mouse
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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.