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

Published

Journal 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.

Full Text

Cited Authors

  • Bohuslav, J; Chen, L-F; Kwon, H; Mu, Y; Greene, WC

Published Date

  • June 2004

Published In

Volume / Issue

  • 279 / 25

Start / End Page

  • 26115 - 26125

PubMed ID

  • 15073170

Pubmed Central ID

  • 15073170

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.m313509200

Language

  • eng