NF-κB at the crossroads of life and death

Abstract

The choice between life and death is one of the major events in regulation of the immune system. T cells that specifically recognize viral or bacterial antigens are selected to survive and proliferate in response to infection, whereas those that are self-reactive are eliminated via apoptosis. Even the survival of alloreactive T cells requires their proper costimulation and, when infection subsides, the activated T cells are eliminated. A major regulator of such life or death decisions is the transcription factor NF-κB. However, NF-κB cannot function alone. A variety of mechanisms exist to modulate its activity and thereby affect the ultimate outcome of a cell's fate.

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Figure 1: IKK can activate NF-κB transcription factors via two distinct pathways.
Figure 2: Signaling cascades used by TNFR1 and Fas to trigger apoptosis.
Figure 3: NF-κB induces a variety of anti-apoptotic factors that can prevent TNF-α–induced apoptosis.

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Acknowledgements

We thank C. Adams for help with manuscript preparation and A. Fornace for disclosing unpublished results. Supported by grants from the National Institutes of Health, the State of California Cancer Research Program and the American Cancer Society.

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Correspondence to Michael Karin.

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Karin, M., Lin, A. NF-κB at the crossroads of life and death. Nat Immunol 3, 221–227 (2002). https://doi.org/10.1038/ni0302-221

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