Role of NF-kappaB in p53-mediated programmed cell death
| Autor: | Karen H. Vousden, Kevin M. Ryan, Mary K. Ernst, Nancy R. Rice |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Programmed cell death
Tumor suppressor gene Apoptosis Biology chemistry.chemical_compound Mice Animals Humans Cloning Molecular Transcription factor Multidisciplinary Cell growth Tumor Necrosis Factor-alpha NF-kappa B Transcription Factor RelA NF-κB DNA Cell biology UVB-induced apoptosis chemistry Cell culture Mutation Cancer research Tumor Suppressor Protein p53 Protein Binding Signal Transduction |
| Zdroj: | Nature. 404(6780) |
| ISSN: | 0028-0836 |
| Popis: | The tumour suppressor p53 inhibits cell growth through activation of cell-cycle arrest and apoptosis, 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. One of the key proteins that modulates the apoptotic response is NF-kappaB, a transcription factor that can protect or contribute to apoptosis. Here we show that induction of p53 causes an activation of NF-kappaB that correlates with the ability of p53 to induce apoptosis. Inhibition or loss of NF-kappaB activity abrogated p53-induced apoptosis, indicating that NF-kappaB is essential in p53-mediated cell death. Activation of NF-kappaB 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-kappaB by p53 and completely abrogated p53-induced cell death. We conclude that inhibition of NF-kappaB in tumours that retain wild-type p53 may diminish, rather than augment, a therapeutic response. |
| Databáze: | OpenAIRE |
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