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1: Genes Dev. 2004 Dec 1;18(23):2905-15. Epub 2004 Nov 15.Click here to read Click here to read Links

JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species.

Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

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.

PMID: 15545623 [PubMed - indexed for MEDLINE]

PMCID: PMC534651