Review

Tumor necrosis factor signaling

  • Cell Death and Differentiation (2003) 10, 4565 (2003)
  • doi:10.1038/sj.cdd.4401189
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Edited by G Melino

Abstract

A single mouse click on the topic tumor necrosis factor (TNF) in PubMed reveals about 50 000 articles providing one or the other information about this pleiotropic cytokine or its relatives. This demonstrates the enormous scientific and clinical interest in elucidating the biology of a molecule (or rather a large family of molecules), which began now almost 30 years ago with the description of a cytokine able to exert antitumoral effects in mouse models. Although our understanding of the multiple functions of TNF in vivo and of the respective underlying mechanisms at a cellular and molecular level has made enormous progress since then, new aspects are steadily uncovered and it appears that still much needs to be learned before we can conclude that we have a full comprehension of TNF biology. This review shortly covers some general aspects of this fascinating molecule and then concentrates on the molecular mechanisms of TNF signal transduction. In particular, the multiple facets of crosstalk between the various signalling pathways engaged by TNF will be addressed.

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Author information

Affiliations

  1. Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany

    • H Wajant
    • , K Pfizenmaier
    •  & P Scheurich

Authors

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  2. Search for K Pfizenmaier in:

  3. Search for P Scheurich in:

Corresponding author

Correspondence to H Wajant.

Glossary

ASK1

apoptosis signal-regulated kinase-1

aSMase

acidic sphingomyelinase

BIR

baculovirus IAP repeat

DD

death domain

DED

death effector domain

DISC

death-inducing signalling complex

FADD

Fas-associated death domain protein

FAN

factor associated with neutral sphingomyelinase activation

GSK

germinal center kinase

IAP

inhibitor of apoptosis protein

IKK

inhibitor of NF-κB kinase

IL

interleukin

I-κB

inhibitor of kappa B

JNK

c-Jun N-terminal kinase

LPS

lipopolysaccharide

LTa

lymphotoxin-a

MAPK

mitogen-activated protein kinase

MEF

mouse embryonic fibroblast

MEKK

mitogen-activated protein kinase/Erk kinase kinase

NEMO

NF-κB essential modulator

NF-κB

nuclear factor kappa B

PARP

poly(ADP-ribose) polymerase

nSMase

neutral sphingomyelinase

PI3K

phosphoinositide-3OH kinase

PKA

protein kinase A

PKB

protein kinase B

PKC

protein kinase C

PLAD

pre-ligand binding assembly domain

PTEN

phosphatase and tensin homologue deleted on chromosome 10

RHD

rel homology domain

RING

really interesting new gene

RIP

receptor-interacting protein

ROS

reactive oxygen species

SAPK

stress-activated protein kinase

TACE

TNF alpha-converting enzyme

SODD

silencer of death domain protein

TANK

TRAF-associated NF-kappaB activator

TNF

tumor necrosis factor

TRADD

TNF receptor-associated death domain protein

TRAF

TNF receptor-associated factor

Trx

thioredoxin