ArticleProceedings of the National Academy of Sciences of the United States of America2010
NLR family member NLRC5 is a transcriptional regulator of MHC class I genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 283 papers, 4 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
283 citing papers in PubMed, 4 syntheses or guidelines pooled it, 425 citations in OpenAlex.
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- Blood DNA methylation sites predict death risk in a longitudinal study of 12, 300 individuals.Aging · 2020Pooled it
- Association of Methylation Signals With Incident Coronary Heart Disease in an Epigenome-Wide Assessment of Circulating Tumor Necrosis Factor α.JAMA cardiology · 2018Pooled it
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- Regulatory NLRs in HSV-1 Infection: Direct Evidence, Comparative Mechanisms and Testable Hypotheses.Pathogens (Basel, Switzerland) · 2026Review
- NLRC5 restricts Japanese encephalitis virus replication and neuroinflammation by interacting with the viral NS3 protein in an IFN-γ-dependent manner.Journal of neuroinflammation · 2026Article
- Long-term major histocompatibility complex class I suppression in astronauts and clinical implications.Communications biology · 2026Review
- In vivo engineering tumor cells to a universal "all-in-one" cancer vaccine with full antigen spectrum.Science advances · 2026Article
- Dihydroartemisinin inhibits mutant KRAS to potentiate regorafenib plus anti-PD-1 in KRAS-mutant colorectal cancer liver metastases.Cell death & disease · 2026Article
- Turep: Detecting cross-cancer tumor-reactive T cells in single-cell and spatial transcriptomics data.bioRxiv : the preprint server for biology · 2026Article
- Messing with Signal 1: How Perturbed MHC Class I Antigen Presentation Contributes to Cancer.Cells · 2026Review
- Upregulation of an Epithelial miRNA Is Associated with Immune Evasion in Progressive Bronchial Premalignant Lesions.Cancer immunology research · 2026Article
- HighCancers · 2026Article
- TGEV activates RIG-I/IFN-β/STAT1 axis to promote NLRC5-mediated SLA-I upregulation.Veterinary research · 2026Article
- Radix Rehmanniae Preparata polysaccharide promoted zebrafish heart regeneration by activating the IFN-γ/NF-κB signaling axis.Biology direct · 2026Article
- Role of Nod-like Receptors inMicroorganisms · 2026Review
- The race between viral immune evasion and the MHC class I antigen processing pathway.FEMS microbiology reviews · 2026Review
- Multifaceted regulation of thymic tolerance by pattern recognition cascades.Frontiers in immunology · 2026Review
- D-xylose suppresses hepatocellular carcinoma progression by regulating dihydrodiol dehydrogenase and remodeling the immune microenvironment.Frontiers in immunology · 2026Article
223 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
MHC class I plays a critical role in the immune defense against viruses and tumors by presenting antigens to CD8 T cells. An NLR protein, class II transactivator (CIITA), is a key regulator of MHC class II gene expression that associates and cooperates with transcription factors in the MHC class II promoter. Although CIITA also transactivates MHC class I gene promoters, loss of CIITA in humans and mice results in the severe reduction of only MHC class II expression, suggesting that additional mechanisms regulate the expression of MHC class I. Here, we identify another member of the NLR protein family, NLRC5, as a transcriptional regulator of MHC class I genes. Similar to CIITA, NLRC5 is an IFN-gamma-inducible nuclear protein, and the expression of NLRC5 resulted in enhanced MHC class I expression in lymphoid as well as epithelial cell lines. Using chromatin immunoprecipitation and reporter gene assays, we show that NLRC5 associates with and activates the promoters of MHC class I genes. Furthermore, we show that the IFN-gamma-induced up-regulation of MHC class I requires NLRC5, because knockdown of NLRC5 specifically impaired the expression of MHC class I. In addition to MHC class I genes, NLRC5 also induced the expression of beta2-microglobulin, transporter associated with antigen processing, and large multifunctional protease, which are essential for MHC class I antigen presentation. Our results suggest that NLRC5 is a transcriptional regulator, orchestrating the concerted expression of critical components in the MHC class I pathway.
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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.