JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species
Open accessAbstract
The c-Jun NH 2-terminal kinase (JNK) has been implicated in both cell death and survival responses to different stimuli. Here we reexamine the function of JNK in tumor necrosis factor (TNF)-stimulated cell death using fibroblasts isolated from wild-type, Mkk4-/-Mkk7-/-, and Jnk1-/-Jnk2-/- mice. We demonstrate that JNK can act to suppress TNF-stimulated apoptosis. However, we find that JNK can also potentiate TNF-stimulated necrosis by increasing the production of reactive oxygen species (ROS). Together, these data indicate that JNK can shift the balance of TNF-stimulated cell death from apoptosis to necrosis. Increased necrosis may represent a contributing factor in stress-induced inflammatory responses mediated by JNK.
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JNK activation shifts the balance of TNF-stimulated cell death from apoptosis to necrosis.
“JNK activation shifts the balance of TNF‐stimulated cell death from apoptosis to necrosis”
From p21 maintains senescent cell viability under persistent DNA damage response by restraining JNK and caspase signaling (2017) · cites this paper as Ventura et al, 2004
Sustained JNK activation shifts TNF-mediated programmed cell death from apoptosis to necrosis.
“This is in line with the finding that sustained JNK activation shifts TNF-mediated programmed cell death from apoptosis to necrosis [217,218] and that heme can trigger necroptosis in Mø, via an autocrine loop in which heme triggers the production of TNF upon the engagement of TLR4 [173].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [218]
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References 43 · Cited by 303
- Authors
- Ventura, J.-J., Cogswell, P., Flavell, R. A., Baldwin, A. S., & Davis, R. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-11-15
- Volume
- 18
- Issue
- 23
- Pages
- 2905-2915
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC534651
- OpenAlex
- W4297970368
- Cited by
- 303
- References
- 43
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 9 · 2022: 8 · 2021: 11 · 2020: 13 · 2019: 13 · 2018: 2 · 2017: 13 · 2016: 11 · 2015: 11 · 2014: 17 · 2013: 19 · 2012: 16
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- eScholarship@UMassChan (submittedVersion)
- UNC Libraries
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (AI35098, DK32520)
- National Cancer Institute (R01CA073756, CA-65861, R01CA065861, CA73756)
- National Institute of Allergy and Infectious Diseases (AI 35098, R37AI035098, R01AI035098)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 32520, P30DK032520)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- c-Jun NH2-terminal kinase, reactive oxygen species, apoptosis, necrosis, MKK4, MKK7, JNK2, fibroblasts, inflammation, stress-induced cell death
- MeSH terms
- Animals, Tumor Necrosis Factor-alpha, Cell Death, Reactive Oxygen Species, Mitogen-Activated Protein Kinase Kinases, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase 4, Mice
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