ArticleGenes & development2009
TNFalpha shedding and epidermal inflammation are controlled by Jun proteins.
Article in Genes & development, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
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- TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.Nature reviews. Rheumatology · 2023Review
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- Tumor necrosis factor-α and matrix metalloproteinase-9 cooperatively exacerbate neurovascular degeneration in the neonatal rat retina.Cell and tissue research · 2022Article
- The Hallmarks of Flavonoids in Cancer.Molecules (Basel, Switzerland) · 2021Review
- Defects in Protein Folding and/or Quality Control Cause Protein Aggregation in the Endoplasmic Reticulum.Progress in molecular and subcellular biology · 2021Article
- Colocalization with MMP-7 in the Distal Colon is Crucial for Syndecan-2 Shedding in Dextran Sulfate Sodium-Induced Colitis Mice.Journal of inflammation research · 2021Article
- Squamous differentiation requires G2/mitosis slippage to avoid apoptosis.Cell death and differentiation · 2020Article
- Functional interactions between Mi-2β and AP1 complexes control response and recovery from skin barrier disruption.The Journal of experimental medicine · 2020Article
- Genetic variants in NECTIN4 encoding an adhesion molecule are associated with continued opioid use.PloS one · 2020Article
- Potential role of a disintegrin and metalloproteinase-17 (ADAM17) in age-associated ventricular remodeling of rats.RSC advances · 2019Article
- Activation of the c-Jun N-terminal kinase pathway aggravates proteotoxicity of hepatic mutant Z alpha1-antitrypsin.Hepatology (Baltimore, Md.) · 2017Article
- A Disintegrin and Metalloprotease 17 in the Cardiovascular and Central Nervous Systems.Frontiers in physiology · 2016Review
- Therapy of psoriasis with narrowband ultraviolet-B light influences plasma concentrations of MMP-2 and TIMP-2 in patients.Therapeutics and clinical risk management · 2016Article
- The microRNA-183 cluster: the family that plays together stays together.Nucleic acids research · 2015Review
- Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2.Genes & development · 2015Article
- Regulation of oxidative stress by methylation-controlled J protein controls macrophage responses to inflammatory insults.The Journal of infectious diseases · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inducible epidermal deletion of JunB and c-Jun in adult mice causes a psoriasis-like inflammatory skin disease. Increased levels of the proinflammatory cytokine TNFalpha play a major role in this phenotype. Here we define the underlying molecular mechanism using genetic mouse models. We show that Jun proteins control TNFalpha shedding in the epidermis by direct transcriptional activation of tissue inhibitor of metalloproteinase-3 (TIMP-3), an inhibitor of the TNFalpha-converting enzyme (TACE). TIMP-3 is down-regulated and TACE activity is specifically increased, leading to massive, cell-autonomous TNFalpha shedding upon loss of both JunB and c-Jun. Consequently, a prominent TNFalpha-dependent cytokine cascade is initiated in the epidermis, inducing severe skin inflammation and perinatal death of newborns from exhaustion of energy reservoirs such as glycogen and lipids. Importantly, this metabolic "cachectic" phenotype can be genetically rescued in a TNFR1-deficient background or by epidermis-specific re-expression of TIMP-3. These findings reveal that Jun proteins are essential physiological regulators of TNFalpha shedding by controlling the TIMP-3/TACE pathway. This novel mechanism describing how Jun proteins control skin inflammation offers potential targets for the treatment of skin pathologies associated with increased TNFalpha levels.
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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.