ArticleArthritis research & therapy2006
Human autoantibodies against the 54 kDa protein of the signal recognition particle block function at multiple stages.
Article in Arthritis research & therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab.Rheumatology (Oxford, England) · 2016Trial
- The Effect of Anti-3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR) Human Autoantibodies on Muscle Regeneration in Mice.Muscle & nerve · 2025Article
- Efgartigimod combined with steroids as a fast-acting therapy for anti-SRP immune-mediated necrotizing myopathy.Frontiers in neurology · 2025Article
- Immune-Mediated Necrotizing Myopathy (IMNM): A Story of Antibodies.Antibodies (Basel, Switzerland) · 2024Review
- Anti-signal recognition particle antibodies induce cardiac diastolic dysfunction via oxidative stress injury.Clinical & translational immunology · 2024Article
- Pathophysiological Mechanisms and Treatment of Dermatomyositis and Immune Mediated Necrotizing Myopathies: A Focused Review.International journal of molecular sciences · 2022Review
- Signal Recognition Particle in Human Diseases.Frontiers in genetics · 2022Article
- The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum.International journal of molecular sciences · 2021Review
- Inositol Signaling in the Basidiomycete FungusJournal of fungi (Basel, Switzerland) · 2021Article
- The Autoantigen Repertoire and the Microbial RNP World.Trends in molecular medicine · 2021Review
- Noncanonical Functions and Cellular Dynamics of the Mammalian Signal Recognition Particle Components.Frontiers in molecular biosciences · 2021Review
- Immune-mediated necrotizing myopathy: clinical features and pathogenesis.Nature reviews. Rheumatology · 2020Review
- RNA packaging into extracellular vesicles: An orchestra of RNA-binding proteins?Journal of extracellular vesicles · 2020Review
- Disease Specific Autoantibodies in Idiopathic Inflammatory Myopathies.Frontiers in neurology · 2019Review
- Potential Pathogenic Role of Anti-Signal Recognition Protein and Anti-3-hydroxy-3-methylglutaryl-CoA Reductase Antibodies in Immune-Mediated Necrotizing Myopathies.Current rheumatology reports · 2018Review
- Article
- Immune-mediated necrotizing myopathy.Zeitschrift fur Rheumatologie · 2016Review
- Autoimmune Myopathies: Where Do We Stand?Frontiers in immunology · 2016Review
- Anti-signal recognition particle autoantibody ELISA validation and clinical associations.Rheumatology (Oxford, England) · 2015Article
- Immune-mediated necrotizing myopathy, associated with antibodies to signal recognition particle, together with lupus nephritis: case presentation and management.Journal of clinical medicine research · 2015Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 4 countries.
Funding
Abstract
The 54 kDa subunit of the signal recognition particle (SRP54) binds to the signal sequences of nascent secretory and membrane proteins and it contributes to the targeting of these precursors to the membrane of the endoplasmic reticulum (ER). At the ER membrane, the binding of the signal recognition particle (SRP) to its receptor triggers the release of SRP54 from its bound signal sequence and the nascent polypeptide is transferred to the Sec61 translocon for insertion into, or translocation across, the ER membrane. In the current article, we have characterized the specificity of anti-SRP54 autoantibodies, which are highly characteristic of polymyositis patients, and investigated the effect of these autoantibodies on the SRP function in vitro. We found that the anti-SRP54 autoantibodies had a pronounced and specific inhibitory effect upon the translocation of the secretory protein preprolactin when analysed using a cell-free system. Our mapping studies showed that the anti-SRP54 autoantibodies bind to the amino-terminal SRP54 N-domain and to the central SRP54 G-domain, but do not bind to the carboxy-terminal M-domain that is known to bind ER signal sequences. Nevertheless, anti-SRP54 autoantibodies interfere with signal-sequence binding to SRP54, most probably by steric hindrance. When the effect of anti-SRP autoantibodies on protein targeting the ER membrane was further investigated, we found that the autoantibodies prevent the SRP receptor-mediated release of ER signal sequences from the SRP54 subunit. This observation supports a model where the binding of the homologous GTPase domains of SRP54 and the alpha-subunit of the SRP receptor to each other regulates the release of ER signal sequences from the SRP54 M-domain.
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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.