NF-κB Antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to Suppress Caspase-8 Activation

Tumor necrosis factor α (TNF-α) binding to the TNF receptor (TNFR) potentially initiates apoptosis and activates the transcription factor nuclear factor kappa B (NF-κB), which suppresses apoptosis by an unknown mechanism. The activation of NF-κB was found to block the activation of caspase-8. TRAF1...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1998-09, Vol.281 (5383), p.1680-1683
Main Authors: Wang, Cun-Yu, Mayo, Marty W., Korneluk, Robert G., Goeddel, David V., Baldwin, Albert S.
Format: Article
Language:English
Subjects:
Ageing, cell death
Antibodies
Apoptosis
Biological and medical sciences
Cell death
Cell lines
Cell physiology
Cytochromes
Fibroblasts
Fundamental and applied biological sciences. Psychology
Mitochondria
Molecular and cellular biology
Monoclonal antibodies
Prevention
RNA
Transcription factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tumor necrosis factor α (TNF-α) binding to the TNF receptor (TNFR) potentially initiates apoptosis and activates the transcription factor nuclear factor kappa B (NF-κB), which suppresses apoptosis by an unknown mechanism. The activation of NF-κB was found to block the activation of caspase-8. TRAF1 (TNFR-associated factor 1), TRAF2, and the inhibitor-of-apoptosis (IAP) proteins c-IAP1 and c-IAP2 were identified as gene targets of NF-κB transcriptional activity. In cells in which NF-κB was inactive, all of these proteins were required to fully suppress TNF-induced apoptosis, whereas c-IAP1 and c-IAP2 were sufficient to suppress etoposide-induced apoptosis. Thus, NF-κB activates a group of gene products that function cooperatively at the earliest checkpoint to suppress TNF-κ-mediated apoptosis and that function more distally to suppress genotoxic agent-mediated apoptosis.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.281.5383.1680