JNK Potentiates TNF-stimulated Necrosis by Increasing the Production of Cytotoxic Reactive Oxygen Species

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2004 Nov 17

PMID 15545623

Citations 130

Authors

Juan-Jose Ventura

Patricia Cogswell

Richard A Flavell

Albert S Baldwin Jr

Roger J Davis

Affiliations

Soon will be listed here.

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.

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