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. 
  • 23


    Mendeley users who have this article in their library.
  • N/A


    Citations of this article.


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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Jan Bohuslav

  • Lin-Feng Chen

  • Hakju Kwon

  • Yajun Mu

  • Warner C Greene

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free