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

2004; Cold Spring Harbor Laboratory Press; Volume: 18; Issue: 23 Linguagem: Inglês

10.1101/gad.1223004

1549-5477

Juan‐José Ventura, Patricia C. Cogswell, Richard A. Flavell, Albert S. Baldwin, Roger J. Davis,

Melanoma and MAPK Pathways

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.