p53 induces NF-kappaB activation by an IkappaB kinase-independent mechanism involving phosphorylation of p65 by ribosomal S6 kinase 1.

  • Bohuslav J
  • Chen L
  • Kwon H
 et al. 
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Abstract

Apoptosis induced by p53 has been proposed to involve activation of the transcription factor NF-kappaB. Here we describe the novel molecular mechanism through which p53 and DNA-damaging agents activate NF-kappaB. NF-kappaB induction by p53 does not occur through classical activation of the IkappaB kinases and degradation of IkappaBalpha. Rather, p53 expression stimulates the serine/threonine kinase ribosomal S6 kinase 1 (RSK1), which in turn phosphorylates the p65 subunit of NF-kappaB. The lower affinity of RSK1-phosphorylated p65 for its negative regulator, IkappaBalpha, decreases IkappaBalpha-mediated nuclear export of shuttling forms of NF-kappaB, thereby promoting the binding and action of NF-kappaB on cognate kappaB enhancers. These findings highlight a rather unusual pathway of NF-kappaB activation, which is utilized by the p53 tumor suppressor.

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Authors

  • Jan Bohuslav

  • Lin-Feng Chen

  • Hakju Kwon

  • Yajun Mu

  • Warner C Greene

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