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


Document Type



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


Life Sciences | Medicine and Health Sciences


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



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

Link to Article in PubMed

PubMed ID