Title
JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species
UMMS Affiliation
Howard Hughes Medical Institute and Program in Molecular Medicine
Publication Date
2004-11-17
Document Type
Article
Subjects
Animals; Cell Death; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Mice; Mitogen-Activated Protein Kinase Kinases; *Reactive Oxygen Species; Tumor Necrosis Factor-alpha
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
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.
DOI of Published Version
10.1101/gad.1223004
Source
Genes Dev. 2004 Dec 1;18(23):2905-15. Epub 2004 Nov 15. Link to article on publisher's site
Journal/Book/Conference Title
Genes and development
Related Resources
PubMed ID
15545623
Repository Citation
Ventura J, Cogswell PC, Flavell RA, Baldwin AS, Davis RJ. (2004). JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species. Open Access Articles. https://doi.org/10.1101/gad.1223004. Retrieved from https://escholarship.umassmed.edu/oapubs/576