Sci. STKE, 25 April 2000
Apoptosis Death by NF-B
Protein p53 is a tumor suppressor that acts by arresting the cell cycle and inducing apoptosis. Ryan et al. show that NF-B activity can be anti-apoptotic or pro-apoptotic depending on the stimulus. Stimulation of NF-B was essential in mediating p53-induced cell death, but stimulation of NF-B was important for inhibiting cell death induced by tumor necrosis factor-α (TNF-α). The data suggest that p53 regulates NF-B by mechanisms distinct from that activated by TNF. p53 activates NF-B by stimulating the mitogen-activated protein kinase, MEK1, which phosphorylates and activates pp90rsk, which could then phosphorylate and inactivate IB leading to NF-B activation. Thus, one possible explanation for the divergent roles of NF-B in the programmed cell death pathways activated by p53 and TNF-α may be the different mechanisms of activation of NF-B. These dual roles for NF-B have important implications for targeting NF-B by chemotherapeutic agents to treat cancer: Inhibiting NF-B in tumors with normal p53 function may actually decrease therapeutic effectiveness, whereas inhibiting NF-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-B in p53-mediated programmed cell death. Nature 404: 892-897. [Online Journal]
Citation: Death by NF-B. Sci. STKE 2000, tw3 (2000).
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