ReviewThe Journal of biological chemistry2020
Evolution, role in inflammation, and redox control of leaderless secretory proteins.
Review in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Oxidative protein folding and CaCellular and molecular life sciences : CMLS · 2026Review
- CNS-targeted NLRP3 Inhibition by NT-0527 confers therapeutic advantage in a CAPS mouse model.Journal of neuroinflammation · 2026Article
- Mitochondria-derived peptides in liver disease: Emerging regulators of hepatic metabolism and therapeutic targets.Hepatology communications · 2026Review
- TRPML3 and TRPML1/3 differentially regulate unconventional MIF secretion through TMED10 and secretory autophagy.Autophagy reports · 2026Article
- ABCA1 Transporter Is Involved in the Secretion of CuZn Superoxide Dismutase (SOD)-1 by Activated Human T Lymphocytes.Antioxidants (Basel, Switzerland) · 2025Article
- Prognostic significance of somatic mutations in myeloid cells of men with chronic heart failure - interaction between loss of Y chromosome and clonal haematopoiesis.European journal of heart failure · 2025Article
- Optimized Monothiol Thioredoxin Derivative (ORP100S) Protects In Vitro and In Vivo from Radiation and Chemotoxicity Without Promoting Tumor Proliferation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Endocytic tethers modulate unconventional GAPDH secretion.Cell surface (Amsterdam, Netherlands) · 2025Article
- A secretome atlas of cardiac fibroblasts from healthy and infarcted mouse hearts.Communications biology · 2025Article
- Integrated analyses of Mendelian randomization, eQTL, and single-cell transcriptome identify CCN3 as a potential biomarker in aortic dissection.Scientific reports · 2024Article
- The endolysosomal system in conventional and unconventional protein secretion.The Journal of cell biology · 2024Review
- Pharmacological Analysis of NLRP3 Inflammasome Inhibitor Sodium [(1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)carbamoyl][(1-methyl-1ACS pharmacology & translational science · 2024Article
- Syntaxin17 Restores Lysosomal Function and Inhibits Pyroptosis Caused by Acinetobacter baumannii.Journal of microbiology (Seoul, Korea) · 2024Article
- Exosomes derived from programmed cell death: mechanism and biological significance.Cell communication and signaling : CCS · 2024Review
- Conventional and Unconventional Protein Secretion in Yeast and Animal Cells.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Unconventional protein secretion (UPS): role in important diseases.Molecular biomedicine · 2023Review
- Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System.Biomedicines · 2022Review
- Unconventional Protein Secretion Dependent on Two Extracellular Vesicles: Exosomes and Ectosomes.Frontiers in cell and developmental biology · 2022Review
- Unconventional Pathways of Protein Secretion: MammalsFrontiers in cell and developmental biology · 2022Review
- Prionoids in amyotrophic lateral sclerosis.Brain communications · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Members of the interleukin (IL)-1 family are key determinants of inflammation. Despite their role as intercellular mediators, most lack the leader peptide typically required for protein secretion. This lack is a characteristic of dozens of other proteins that are actively and selectively secreted from living cells independently of the classical endoplasmic reticulum-Golgi exocytic route. These proteins, termed leaderless secretory proteins (LLSPs), comprise proteins directly or indirectly involved in inflammation, including cytokines such as IL-1β and IL-18, growth factors such as fibroblast growth factor 2 (FGF2), redox enzymes such as thioredoxin, and proteins most expressed in the brain, some of which participate in the pathogenesis of neurodegenerative disorders. Despite much effort, motifs that promote LLSP secretion remain to be identified. In this review, we summarize the mechanisms and pathophysiological significance of the unconventional secretory pathways that cells use to release LLSPs. We place special emphasis on redox regulation and inflammation, with a focus on IL-1β, which is secreted after processing of its biologically inactive precursor pro-IL-1β in the cytosol. Although LLSP externalization remains poorly understood, some possible mechanisms have emerged. For example, a common feature of LLSP pathways is that they become more active in response to stress and that they involve several distinct excretion mechanisms, including direct plasma membrane translocation, lysosome exocytosis, exosome formation, membrane vesiculation, autophagy, and pyroptosis. Further investigations of unconventional secretory pathways for LLSP secretion may shed light on their evolution and could help advance therapeutic avenues for managing pathological conditions, such as diseases arising from inflammation.
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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.