The NF-kappaB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease.
NF-kappaB/Rel transcription factors have recently emerged as crucial regulators of cell survival. Activation of NF-kappaB antagonizes programmed cell death (PCD) induced by tumor necrosis factor-receptors (TNF-Rs) and several other triggers. This prosurvival activity of NF-kappaB participates in a wide range of biological processes, including immunity, lymphopoiesis and development. It is also crucial for pathogenesis of various cancers, chronic inflammation and certain hereditary disorders. This participation of NF-kappaB in survival signaling often involves an antagonism of PCD triggered by TNF-R-family receptors, and is mediated through a suppression of the formation of reactive oxygen species (ROS) and a control of sustained activation of the Jun-N-terminal kinase (JNK) cascade. Effectors of this antagonistic activity of NF-kappaB on this ROS/JNK pathway have been recently identified. Indeed, further delineating the mechanisms by which NF-kappaB promotes cell survival might hold the key to developing new highly effective therapies for treatment of widespread human diseases.
Papa
S
S
The Ben May Institute for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Bubici
C
C
Zazzeroni
F
F
Pham
C G
CG
Kuntzen
C
C
Knabb
J R
JR
Dean
K
K
Franzoso
G
G
D000818:Animals; D017209:Apoptosis; D004194:Disease; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006262:Health; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D009336:Necrosis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases