The following article requires a subscription:



(Format: HTML)

The tumour suppressor p53 inhibits cell growth through activation of cell-cycle arrest and apoptosis 1, and most cancers have either mutation within the p53 gene or defects in the ability to induce p53. Activation or re-introduction of p53 induces apoptosis in many tumour cells and may provide effective cancer therapy 2. One of the key proteins that modulates the apoptotic response is NF-[kappa]B, a transcription factor that can protect or contribute to apoptosis 3. Here we show that induction of p53 causes an activation of NF-[kappa]B that correlates with the ability of p53 to induce apoptosis. Inhibition or loss of NF-[kappa]B activity abrogated p53-induced apoptosis, indicating that NF-[kappa]B is essential in p53-mediated cell death. Activation of NF-[kappa]B by p53 was distinct from that mediated by tumour-necrosis factor-[alpha] and involved MEK1 and the activation of pp90rsk. Inhibition of MEK1 blocked activation of NF-[kappa]B by p53 and completely abrogated p53-induced cell death. We conclude that inhibition of NF-[kappa]B in tumours that retain wild-type p53 may diminish, rather than augment, a therapeutic response.

(C) 2000 Nature Publishing Group