ArticleThe Journal of biological chemistry2017
Assembly-induced folding regulates interleukin 12 biogenesis and secretion.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- The active secretion of a subunit of IL-12 by tissue cells is regulated by Valosin-Containing Protein and intracellular calcium redistribution.bioRxiv : the preprint server for biology · 2026Article
- Changes in Serum IL-12 Levels following the Administration of H1-Antihistamines in Patients with Chronic Spontaneous Urticaria.Journal of personalized medicine · 2024Article
- Next generation of multispecific antibody engineering.Antibody therapeutics · 2024Review
- Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions.Science advances · 2023Article
- HLJ1 amplifies endotoxin-induced sepsis severity by promoting IL-12 heterodimerization in macrophages.eLife · 2022Article
- Non-autophagy Role of Atg5 and NBR1 in Unconventional Secretion of IL-12 Prevents Gut Dysbiosis and Inflammation.Journal of Crohn's & colitis · 2022Article
- Interleukin-35: Structure, Function and Its Impact on Immune-Related Diseases.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2021Review
- The subunits of IL-12, originating from two distinct cells, can functionally synergize to protect against pathogen dissemination in vivo.Cell reports · 2021Article
- A Chaperone-Like Role for EBI3 in Collaboration With Calnexin Under Inflammatory Conditions.Frontiers in immunology · 2021Review
- Stimulus-Specific Expression, Selective Generation and Novel Function of Grass Carp (Frontiers in immunology · 2021Article
- IL-12 and IL-23-Close Relatives with Structural Homologies but Distinct Immunological Functions.Cells · 2020Review
- Site-Specific Protein Labeling with Fluorophores as a Tool To Monitor Protein Turnover.Chembiochem : a European journal of chemical biology · 2020Article
- A folding switch regulates interleukin 27 biogenesis and secretion of its α-subunit as a cytokine.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Long Interleukin-22 Binding Protein Isoform-1 Is an Intracellular Activator of the Unfolded Protein Response.Frontiers in immunology · 2018Article
- Genome-Wide Characterization of Selection Signatures and Runs of Homozygosity in Ugandan Goat Breeds.Frontiers in genetics · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Members of the IL-12 family perform essential functions in immunoregulation by connecting innate and adaptive immunity and are emerging therapeutic targets. They are unique among other interleukins in forming heterodimers that arise from extensive subunit sharing within the family, leading to the production of at least four functionally distinct heterodimers from only five subunits. This raises important questions about how the assembly of IL-12 family members is regulated and controlled in the cell. Here, using cell-biological approaches, we have dissected basic principles that underlie the biogenesis of the founding member of the family, IL-12. Within the native IL-12 heterodimer, composed of IL-12α and IL-12β, IL-12α possesses three intramolecular and one intermolecular disulfide bridges. We show that, in isolation, IL-12α fails to form its native structure but, instead, misfolds, forming incorrect disulfide bonds. Co-expression of its β subunit inhibits misfolding and thus allows secretion of biologically active heterodimeric IL-12. On the basis of these findings, we identified the disulfide bonds in IL-12α that are critical for assembly-induced secretion and biological activity of IL-12
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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.