The ING4 Tumor Suppressor Attenuates NF-κB Activity at the Promoters of Target Genes
- 1 November 2008
- journal article
- research article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 28 (21), 6632-6645
- https://doi.org/10.1128/mcb.00697-08
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.Keywords
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