HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 1, 244-252, January 7, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/1/244    most recent M409344200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Anrather, J. Articles by Iadecola, C. Search for Related Content PubMed PubMed Citation Articles by Anrather, J. Articles by Iadecola, C. Social Bookmarking                      What's this?

cis-Acting Element-specific Transcriptional Activity of Differentially Phosphorylated Nuclear Factor-B^*

Josef Anrather, Gianfranco Racchumi, and Costantino Iadecola

From the Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021

Phosphorylation of nuclear factor-B (NF-B) subunits emerges as a mechanism by which transcriptional activity of nuclear NF-B complexes is regulated in an inhibitor B-independent fashion. As the main transactivator, the p65 subunit of NF-B has an outstanding position in the hierarchy of NF-B proteins. p65 is a multiply phosphorylated protein with phosphorylation sites in the C-terminal transactivation domain and the N-terminal Rel homology domain (RHD). In this study, we describe two previously non-reported phospho-acceptor sites within the p65 RHD. We show that differential phosphorylation of serine residues within the RHD modulates transcriptional activity in a cis-acting element and promoter-specific context, thus leading to a phosphorylation state-dependent gene expression profile. RelA^-/- mouse embryonic fibroblasts reconstituted with wild-type p65 or p65 phosphorylation-deficient mutants showed a distinctive expression profile of synthetic B-dependent reporters as well as endogenous genes. Hypophosphorylated p65 did not display cis-acting element-specific changes in DNA binding or dimerization behavior. This study shows for the first time that site-specific phosphorylation can target a transcription factor to a particular subset of genes.

Received for publication, August 16, 2004 , and in revised form, October 12, 2004.

^* This work was supported by National Institute of Health Grant HL59476 (to J. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: 411 East 69th St., Rm. KB410, New York, NY 10021. E-mail: joa2006{at}med.cornell.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Yao, S.-R. Yang, I. Edirisinghe, S. Rajendrasozhan, S. Caito, D. Adenuga, M. A. O'Reilly, and I. Rahman Disruption of p21 Attenuates Lung Inflammation Induced by Cigarette Smoke, LPS, and fMLP in Mice Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 7 - 18. [Abstract] [Full Text] [PDF]

				D. E. Nowak, B. Tian, M. Jamaluddin, I. Boldogh, L. A. Vergara, S. Choudhary, and A. R. Brasier RelA Ser276 Phosphorylation Is Required for Activation of a Subset of NF-{kappa}B-Dependent Genes by Recruiting Cyclin-Dependent Kinase 9/Cyclin T1 Complexes Mol. Cell. Biol., June 1, 2008; 28(11): 3623 - 3638. [Abstract] [Full Text] [PDF]

				T. Kreslavsky, A. I. Garbe, A. Krueger, and H. von Boehmer T cell receptor-instructed {alpha}{beta} versus {gamma}{delta} lineage commitment revealed by single-cell analysis J. Exp. Med., May 12, 2008; 205(5): 1173 - 1186. [Abstract] [Full Text] [PDF]

				H. Yao, I. Edirisinghe, S.-R. Yang, S. Rajendrasozhan, A. Kode, S. Caito, D. Adenuga, and I. Rahman Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice Am. J. Pathol., May 1, 2008; 172(5): 1222 - 1237. [Abstract] [Full Text] [PDF]

				M. P. Seldon, G. Silva, N. Pejanovic, R. Larsen, I. P. Gregoire, J. Filipe, J. Anrather, and M. P. Soares Heme Oxygenase-1 Inhibits the Expression of Adhesion Molecules Associated with Endothelial Cell Activation via Inhibition of NF-{kappa}B RelA Phosphorylation at Serine 276 J. Immunol., December 1, 2007; 179(11): 7840 - 7851. [Abstract] [Full Text] [PDF]

				J. Partridge, H. Carlsen, K. Enesa, H. Chaudhury, M. Zakkar, L. Luong, A. Kinderlerer, M. Johns, R. Blomhoff, J. C. Mason, et al. Laminar shear stress acts as a switch to regulate divergent functions of NF-{kappa}B in endothelial cells FASEB J, November 1, 2007; 21(13): 3553 - 3561. [Abstract] [Full Text] [PDF]

				B. Yamini, X. Yu, M. E. Dolan, M. H. Wu, D. W. Kufe, and R. R. Weichselbaum Inhibition of Nuclear Factor-{kappa}B Activity by Temozolomide Involves O6-Methylguanine Induced Inhibition of p65 DNA Binding Cancer Res., July 15, 2007; 67(14): 6889 - 6898. [Abstract] [Full Text] [PDF]

				V. Gupta, G. Yeo, H. Kawakubo, V. Rangnekar, P. Ramaswamy, T. Hayashida, D. T. MacLaughlin, P. K. Donahoe, and S. Maheswaran Mullerian-Inhibiting Substance Induces Gro-{beta} Expression in Breast Cancer Cells through a Nuclear Factor-{kappa}B-Dependent and Smad1-Dependent Mechanism Cancer Res., March 15, 2007; 67(6): 2747 - 2756. [Abstract] [Full Text] [PDF]

				S. F. Liu and A. B. Malik NF-{kappa}B activation as a pathological mechanism of septic shock and inflammation Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L622 - L645. [Abstract] [Full Text] [PDF]

				J. Anrather, G. Racchumi, and C. Iadecola NF-{kappa}B Regulates Phagocytic NADPH Oxidase by Inducing the Expression of gp91phox J. Biol. Chem., March 3, 2006; 281(9): 5657 - 5667. [Abstract] [Full Text] [PDF]

				E. B. Hammar, J.-C. Irminger, K. Rickenbach, G. Parnaud, P. Ribaux, D. Bosco, D. G. Rouiller, and P. A. Halban Activation of NF-{kappa}B by Extracellular Matrix Is Involved in Spreading and Glucose-stimulated Insulin Secretion of Pancreatic Beta Cells J. Biol. Chem., August 26, 2005; 280(34): 30630 - 30637. [Abstract] [Full Text] [PDF]