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Cell Death & Differentiation
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The NF-κB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease

Cell Death & Differentiationvolume 13, pages712–729 (2006)Cite this article

Abstract

NF-κB/Rel transcription factors have recently emerged as crucial regulators of cell survival. Activation of NF-κB antagonizes programmed cell death (PCD) induced by tumor necrosis factor-receptors (TNF-Rs) and several other triggers. This prosurvival activity of NF-κB 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-κB 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-κB on this ROS/JNK pathway have been recently identified. Indeed, further delineating the mechanisms by which NF-κB promotes cell survival might hold the key to developing new highly effective therapies for treatment of widespread human diseases.

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Abbreviations

PCD:

programmed cell death

NF-κB:

nuclear factor-κB

TNF-α:

tumor necrosis factor-α

TNF-Rs:

tumor necrosis factor-receptors

ROS:

reactive oxygen species

JNK:

Jun-N-terminal kinase

DRs:

death receptors

MAPK:

mitogen-activated protein kinase

IKK:

IκB kinase

LPS:

lipopolysaccharide

TRADD:

TNFR1-associated death-domain protein

TRAF:

TNF-R-associated factor

RIP:

receptor-interacting protein

FADD:

Fas-associated death domain

MAPK:

mitogen-activated protein kinase

MAP2K:

MAPK kinase

MAP3K:

MAPK kinase kinase

MKP:

MAP kinase phosphatase

Gadd45:

growth arrest and DNA damage-inducing 45 protein

Mn-SOD:

manganese-dependent superoxide dismutase

FHC:

ferritin heavy chain

XIAP:

X chromosome-linked inhibitor of apoptosis

MEFs:

murine embryonic fibroblasts

Con A:

concavalin A

BHA:

butylated hydroxylanisole

NAC:

N-acetyl cystein

PDTC:

pyrrolidine dithiocarbamate

MM:

multiple myeloma

HL:

Hodgkin's lymphoma

DLBCL:

diffuse large B-cell lymphoma

CML:

chronic myelogenous leukemia

ALL:

acute lymphoblastic leukemia

IBD:

inflammatory bowel disease

RA:

rheumatoid arthritis

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Acknowledgements

We thank L Sherman for helping with manuscript preparation. This research was supported in part by NIH grants R01-CA84040 and R01-CA098583.

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  1. F Zazzeroni

    Present address: Department of Experimental Medicine, The University of L'Aquila, Via Vetoio-Coppito 2, 67100, L'Aquila, Italy

Authors and Affiliations

  1. The Ben May Institute for Cancer Research, The University of Chicago, IL, Chicago, USA

    S Papa, C Bubici, F Zazzeroni, C G Pham, C Kuntzen, J R Knabb, K Dean & G Franzoso

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Correspondence toG Franzoso.

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Edited by G Kroemer

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Papa, S., Bubici, C., Zazzeroni, F.et al. The NF-κB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease.Cell Death Differ13, 712–729 (2006). https://doi.org/10.1038/sj.cdd.4401865

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