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Sci. STKE, 25 April 2000
Vol. 2000, Issue 29, p. tw3
[DOI: 10.1126/scisignal.292000tw3]

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Apoptosis Death by NF-{kappa}B

Protein p53 is a tumor suppressor that acts by arresting the cell cycle and inducing apoptosis. Ryan et al. show that NF-{kappa}B activity can be anti-apoptotic or pro-apoptotic depending on the stimulus. Stimulation of NF-{kappa}B was essential in mediating p53-induced cell death, but stimulation of NF-{kappa}B was important for inhibiting cell death induced by tumor necrosis factor-α (TNF-α). The data suggest that p53 regulates NF-{kappa}B by mechanisms distinct from that activated by TNF. p53 activates NF-{kappa}B by stimulating the mitogen-activated protein kinase, MEK1, which phosphorylates and activates pp90rsk, which could then phosphorylate and inactivate I{kappa}B leading to NF-{kappa}B activation. Thus, one possible explanation for the divergent roles of NF-{kappa}B in the programmed cell death pathways activated by p53 and TNF-α may be the different mechanisms of activation of NF-{kappa}B. These dual roles for NF-{kappa}B have important implications for targeting NF-{kappa}B by chemotherapeutic agents to treat cancer: Inhibiting NF-{kappa}B in tumors with normal p53 function may actually decrease therapeutic effectiveness, whereas inhibiting NF-{kappa}B in cells with mutated p53 may increase therapeutic effectiveness.

Ryan, K.M., Ernst, M.K., Rice, N.R., and Vousden, K.H. (2000) Role of NF-{kappa}B in p53-mediated programmed cell death. Nature 404: 892-897. [Online Journal]

Citation: Death by NF-{kappa}B. Sci. STKE 2000, tw3 (2000).

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