This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nozell, S. Articles by Benveniste, E. N. Search for Related Content PubMed PubMed Citation Articles by Nozell, S. Articles by Benveniste, E. N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2008, p. 6632-6645, Vol. 28, No. 21
0270-7306/08/$08.00+0     doi:10.1128/MCB.00697-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The ING4 Tumor Suppressor Attenuates NF-B Activity at the Promoters of Target Genes ^,

Susan Nozell,^1* Travis Laver,¹ Dorothy Moseley,¹ Lisa Nowoslawski,¹ Marijke DeVos,¹ George P. Atkinson,¹ Keith Harrison,² L. Burton Nabors,³ and Etty N. Benveniste¹

Departments of Cell Biology,¹ Pathology,² Neurology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005³

Received 29 April 2008/ Returned for modification 7 July 2008/ Accepted 28 August 2008

The NF-B family mediates immune and inflammatory responses. In many cancers, NF-B 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-B is constitutively activated, ING4 expression is negligible, and NF-B-regulated gene expression is elevated. We demonstrate that an ING4 and NF-B interaction exists but does not prevent NF-B activation, nuclear translocation, or DNA binding. Instead, ING4 and NF-B bind simultaneously at NF-B-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-B target gene expression. Collectively, these data suggest that ING4 may specifically regulate the activity of NF-B molecules that are bound to target gene promoters.

---

* Corresponding author. Mailing address: Department of Cell Biology, 1918 University Blvd., MCLM 313, University of Alabama at Birmingham, Birmingham, AL 35294-0005. Phone: (205) 996-9468. Fax: (205) 975-5648. E-mail: snozell{at}uab.edu

Published ahead of print on 8 September 2008.

Supplemental material for this article may be found at http://mcb.asm.org/.

---

Molecular and Cellular Biology, November 2008, p. 6632-6645, Vol. 28, No. 21
0270-7306/08/$08.00+0     doi:10.1128/MCB.00697-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.