Role of NF-kB in p53-mediated programmed cell death

Source: Nature /Vol 404/20 April 2000 

Author: Kevin M. Ryan, Mary K. Ernst, Nancy R. Rice & Karen H. Vousden

Date : 2000/5/24/

Speaker :盧文偉 (g884236)

Abstract :

The tumor suppressor p53 has been implicated in the activation of both death-receptor and Apaf-1-independent apoptosis. Activation or re-introduction of p53 induces apoptosis in many tumor. One of the key proteins that modulates the apoptotic response is NF-kB, a transcription factor that can protect or contribute to apoptosis. In this study, they show that induction of p53 causes an activation of NF-kB  that correlates with the ability of p53 to induce apoptosis. They show that inhibition or loss of NF-kB activity specifically abrogated the p53-mediated apoptotic response, indicating that NF-kB is essential in p53-mediated cell death.
Their results reveal an unexpected pro-apoptotic activity of NF-kB in p53-mediated apoptotic response. Therefore, activation of NF-kB  by p53 was distinct from that mediated by tumour-necross factor-a and involed MEK1 and the activation of pp90rsk. Inhibition of MEK1 blocked activation of NF-kB by p53 and completely abrogated p53-induced cell death. They conclude that inhibition of NF-kB in tumors that retains wild-type p53 may diminish, rather than augment, a therapeutic response.


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