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

Susan Nozell*, Travis Laver, Dorothy Moseley, Lisa Nowoslawski, Marijke DeVos, George P. Atkinson, Keith Harrison, L. Burton Nabors, Etty N. Benveniste

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6632-6645
Number of pages14
JournalMolecular and cellular biology
Volume28
Issue number21
DOIs
StatePublished - Nov 2008
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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