Journal
JOURNAL OF CELL SCIENCE
Volume 117, Issue 22, Pages 5197-5208Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.01483
Keywords
NF-kappa B; JNK; Gadd45 beta; TNF-alpha; apoptosis
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Funding
- NCI NIH HHS [R01-CA098583, R01-CA84040] Funding Source: Medline
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In addition to marshalling immune and inflammatory responses, transcription factors of the NF-kappaB family control cell survival. This control is crucial to a wide range of biological processes, including B and T lymphopoiesis, adaptive immunity, oncogenesis and cancer chemoresistance. During an inflammatory response, NF-kappaB activation antagonizes apoptosis induced by tumor necrosis factor (TNF)-alpha, a protective activity that involves suppression of the Jun N-terminal kinase (JNK) cascade. This suppression can involve upregulation of the Gadd45-family member Gadd45beta/Myd118, which associates with the JNK kinase MKK7/JNKK2 and blocks its catalytic activity. Upregulation of XIAP, A20 and blockers of reactive oxygen species (ROS) appear to be important additional means by which NF-kappaB blunts JNK signaling. These recent findings might open up entirely new avenues for therapeutic intervention in chronic inflammatory diseases and certain cancers; indeed, the Gadd45beta-MKK7 interaction might be a key target for such intervention.
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