ArticleThe Journal of biological chemistry2010
Extended anti-inflammatory action of a degradation-resistant mutant of cell-penetrating suppressor of cytokine signaling 3.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Genome-wide identification of socs gene in rainbow trout (Oncorhynchus mykiss) and response to microplastic exposure.Molecular biology reports · 2025Article
- Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells.Cell reports · 2024Article
- Corneal application of SOCS1/3 peptides for the treatment of eye diseases mediated by inflammation and oxidative stress.Frontiers in immunology · 2024Review
- Suppressor of cytokine signaling 3-derived peptide as a therapeutic for inflammatory and oxidative stress-induced damage to the retina.Molecular vision · 2023Article
- SOCS-JAK-STAT inhibitors and SOCS mimetics as treatment options for autoimmune uveitis, psoriasis, lupus, and autoimmune encephalitis.Frontiers in immunology · 2023Review
- Socs3b regulates the development and function of innate immune cells in zebrafish.Frontiers in immunology · 2023Article
- Corneal Application of R9-SOCS1-KIR Peptide Alleviates Endotoxin-Induced Uveitis.Translational vision science & technology · 2021Article
- SOCS Proteins in Immunity, Inflammatory Diseases, and Immune-Related Cancer.Frontiers in medicine · 2021Review
- Decoding inflammation, its causes, genomic responses, and emerging countermeasures.Scandinavian journal of immunology · 2019Review
- SOCS3 treatment prevents the development of alopecia areata by inhibiting CD8+ T cell-mediated autoimmune destruction.Oncotarget · 2017Article
- SOCS Proteins as Regulators of Inflammatory Responses Induced by Bacterial Infections: A Review.Frontiers in microbiology · 2017Review
- SOCS3 revisited: a broad regulator of disease, now ready for therapeutic use?Cellular and molecular life sciences : CMLS · 2016Review
- New paradigms in sepsis: from prevention to protection of failing microcirculation.Journal of thrombosis and haemostasis : JTH · 2015Review
- Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer's disease brains and human microglia.Neuroscience · 2015Article
- Regulation of Macrophage, Dendritic Cell, and Microglial Phenotype and Function by the SOCS Proteins.Frontiers in immunology · 2015Review
- The adaptor CRADD/RAIDD controls activation of endothelial cells by proinflammatory stimuli.The Journal of biological chemistry · 2014Article
- Role of Ubiquitylation in Controlling Suppressor of Cytokine Signalling 3 (SOCS3) Function and Expression.Cells · 2014Article
- SOCS3, a Major Regulator of Infection and Inflammation.Frontiers in immunology · 2014Review
- Nuclear transport modulation reduces hypercholesterolemia, atherosclerosis, and fatty liver.Journal of the American Heart Association · 2013Article
- Lethality in a murine model of pulmonary anthrax is reduced by combining nuclear transport modifier with antimicrobial therapy.PloS one · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Suppressor of cytokine signaling 3 (SOCS3) regulates the proinflammatory cytokine signaling mediated by the JAK/STAT signaling pathway. SOCS3 is rapidly induced and then targeted to the ubiquitin-proteasome pathway via a mechanism that requires the C-terminal SOCS box. Due to its rapid turnover, the intracellular stores of SOCS3 seem insufficient to control acute or protracted inflammatory diseases. Previously, we developed an intracellular protein therapy that uses a recombinant cell-penetrating form of SOCS3 (CP-SOCS3) to inhibit the JAK/STAT pathway and prevent cytokine-mediated lethal inflammation and apoptosis of the liver (Jo, D., Liu, D., Yao, S., Collins, R. D., and Hawiger, J. (2005) Nat. Med. 11, 892-898). The potent anti-inflammatory and cytoprotective activity of CP-SOCS3 prompted us to analyze its intracellular turnover, as compared with that of endogenous SOCS3 protein induced in macrophages by the proinflammatory agonists, interferon-gamma and lipopolysaccharide. We found that the half-life (t(1/2)) of endogenous SOCS3 is 0.7 h in activated macrophages, compared with a t(1/2) of 6.2 h for recombinant CP-SOCS3. Deletion of the SOCS box in CP-SOCS3 renders it more resistant to proteasomal degradation, extending its t(1/2) to 29 h. Consequently, this SOCS box-deleted form of CP-SOCS3 displays persistent inhibitory activity for 24 h toward interferon-gamma- and lipopolysaccharide-induced cytokine and chemokine production. Compared with the wild-type suppressor, this gain-of-function CP-SOCS3 mutant provides a longer acting inhibitor of cytokine signaling, a feature that offers a clear advantage for the intracellular delivery of proteins to treat acute or protracted inflammatory diseases.
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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.