p53 induces NF-κB activation by an IκB kinase-independent mechanism involving phosphorylation of p65 by ribosomal S6 kinase 1

Jan Bohuslav, Lin Feng Chen, Hakju Kwon, Yajun Mu, Warner C. Greene

Research output: Contribution to journalArticlepeer-review

Abstract

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

Original languageEnglish (US)
Pages (from-to)26115-26125
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number25
DOIs
StatePublished - Jun 18 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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