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Suppression of TNF-alpha-induced apoptosis by NF-kappaB
D J Van Antwerp1, S J Martin, T Kafri
1Laboratory of Genetics, Salk Institute, La Jolla, CA 92037, USA. Jolla Institute for Allergy and Immu.
Abstract:
Tumor necrosis factor alpha (TNF-alpha) signaling gives rise to a number of events, including activation of transcription factor NF-kappaB and programmed cell death (apoptosis). Previous studies of TNF-alpha signaling have suggested that these two events occur independently. The sensitivity and kinetics of TNF-alpha-induced apoptosis are shown to be enhanced in a number of cell types expressing a dominant-negative IkappaBalpha (IkappaBalphaM). These findings suggest that a negative feedback mechanism results from TNF-alpha signaling in which NF-kappaB activation suppresses the signals for cell death.
Insights
Tumor necrosis factor alpha (TNF-alpha) signaling activates NF-kappaB and apoptosis. Enhanced apoptosis in cells with IkappaBalphaM suggests NF-kappaB activation suppresses cell death signals.
Area of Science:
- Cellular biology
- Molecular signaling pathways
Background:
- Tumor necrosis factor alpha (TNF-alpha) signaling triggers key cellular events like NF-kappaB activation and apoptosis.
- Previous research indicated independent pathways for TNF-alpha-induced NF-kappaB activation and apoptosis.
Purpose of the Study:
- To investigate the relationship between TNF-alpha signaling, NF-kappaB activation, and apoptosis.
- To explore the role of IkappaBalpha in modulating TNF-alpha-induced cell death.
Main Methods:
- Utilized cell types expressing a dominant-negative IkappaBalpha (IkappaBalphaM).
- Analyzed the sensitivity and kinetics of TNF-alpha-induced apoptosis in these cells.
Main Results:
- Cells expressing IkappaBalphaM exhibited enhanced sensitivity and altered kinetics of TNF-alpha-induced apoptosis.
- The findings indicate that NF-kappaB activation influences the apoptotic response to TNF-alpha.
Conclusions:
- TNF-alpha signaling involves a negative feedback loop where NF-kappaB activation suppresses cell death signals.
- IkappaBalpha plays a crucial role in this feedback mechanism, modulating apoptosis sensitivity.