The ING4 tumor suppressor attenuates NF-κB activity at the promoters of target genes

Academic Article

Abstract

  • The NF-κB family mediates immune and inflammatory responses. In many cancers, NF-κB is constitutively activated and induces the expression of genes that facilitate tumorigenesis. ING4 is a tumor suppressor that is absent or mutated in several cancers. Herein, we demonstrate that in human gliomas, NF-κB is constitutively activated, ING4 expression is negligible, and NF-κB-regulated gene expression is elevated. We demonstrate that an ING4 and NF-κB interaction exists but does not prevent NF-κB activation, nuclear translocation, or DNA binding. Instead, ING4 and NF-κB bind simultaneously at NF-κB-regulated promoters, and this binding correlates with reductions in p65 phosphorylation, p300, and the levels of acetylated histones and H3-Me3K4, while enhancing the levels of HDAC-1 at these promoters. Using a knockdown approach, we correlate reductions in ING4 protein levels with increased basal and inducible NF-κB target gene expression. Collectively, these data suggest that ING4 may specifically regulate the activity of NF-κB molecules that are bound to target gene promoters. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Nozell S; Laver T; Moseley D; Nowoslawski L; DeVos M; Atkinson GP; Harrison K; Nabors LB; Benveniste EN
  • Start Page

  • 6632
  • End Page

  • 6645
  • Volume

  • 28
  • Issue

  • 21