ArticleJournal of immunology (Baltimore, Md. : 1950)2014
The differential regulation of human ACT1 isoforms by Hsp90 in IL-17 signaling.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Pharmacological Mechanisms of CheReCunJin Formula in Ameliorating Sjögren's Syndrome: Suppression of IL-17 Signal-Mediated Inflammatory Cascade.Journal of inflammation research · 2025Article
- Molecular consideration relevant to the mechanism of the comorbidity between psoriasis and systemic lupus erythematosus (Review).Experimental and therapeutic medicine · 2023Review
- TRAF3IP2-IL-17 Axis Strengthens the Gingival Defense against Pathogens.Journal of dental research · 2023Article
- Transcriptional Basis of Psoriasis from Large Scale Gene Expression Studies: The Importance of Moving towards a Precision Medicine Approach.International journal of molecular sciences · 2022Review
- Maximizing the Utility of Transcriptomics Data in Inflammatory Skin Diseases.Frontiers in immunology · 2021Review
- Low Levels of Vitamin D Promote Memory B Cells in Lupus.Nutrients · 2020Article
- Neutrophil Extracellular Traps Induce Human Th17 Cells: Effect of Psoriasis-Associated TRAF3IP2 Genotype.The Journal of investigative dermatology · 2019Article
- Adaptive and Innate Immunity in Psoriasis and Other Inflammatory Disorders.Frontiers in immunology · 2019Review
- Act1 is a negative regulator in T and B cells via direct inhibition of STAT3.Nature communications · 2018Article
- Plasma CXCL1 levels and TRAF3IP2 variants in patients with myocardial infarction.Journal of clinical laboratory analysis · 2018Article
- Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis.Scientific reports · 2018Article
- IL-17: overview and role in oral immunity and microbiome.Oral diseases · 2017Review
- Current knowledge on psoriasis and autoimmune diseases.Psoriasis (Auckland, N.Z.) · 2016Review
- Genetic Factors in Systemic Lupus Erythematosus: Contribution to Disease Phenotype.Journal of immunology research · 2015Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
IL-17 is a proinflammatory cytokine implicated in the pathogenesis of autoimmune diseases including psoriasis. ACT1 is an essential adaptor molecule in the IL-17 signaling pathway. A missense single nucleotide polymorphism (rs33980500; SNP-D10N) that resulted in the substitution of an asparagine for an aspartic acid at position 10 of ACT1 (ACT1-D10N) is associated with psoriasis susceptibility. Due to alternative splicing in humans, SNP-D10N encodes two mutated ACT1 proteins, ACT1-D10N and ACT1-D19N. Although both ACT1 isoforms are Hsp90 client proteins, the nine additional amino acids in ACT1-D19N provide an additional Hsp90 binding site that is absent in ACT1-D10N. Therefore, whereas ACT1-D10N is a dead protein that is unable to transduce IL-17 signals for gene expression, ACT1-D19N is fully responsive to IL-17. Intriguingly, the two ACT1 isoforms are differentially expressed in ACT1(D10N/D10N) fibroblasts and T cells. Fibroblasts express both isoforms equally, enabling ACT1-D19N to compensate for the loss of ACT1-D10N function. ACT1(D10N/D10N) T cells, however, express predominantly ACT1-D10N. Lacking this compensatory mechanism, ACT1(D10N/D10N) T cells behave like ACT1-deficient T cells, exhibiting a dysregulated and hyperactive Th17 phenotype with overproduction of IL-22 and IL-17. The hyperactive Th17 response combined with fully responsive fibroblasts likely synergized to contribute to psoriasis susceptibility in SNP-D10N patients.
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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.