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

J. Biol. Chem., Vol. 282, Issue 22, 15981-15994, June 1, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/22/15981    most recent M608979200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xu, Y. Articles by St. Clair, D. K. Search for Related Content PubMed PubMed Citation Articles by Xu, Y. Articles by St. Clair, D. K. Social Bookmarking                      What's this?

The Role of a Single-stranded Nucleotide Loop in Transcriptional Regulation of the Human sod2 Gene^*

Yong Xu, Fang Fang, Sanjit K. Dhar, William H. St. Clair, Edward J. Kasarskis^¶, and Daret K. St. Clair¹

From the Graduate Center for Toxicology, the Department of Radiation Medicine, and the ^¶Department of Neurology, University of Kentucky, Lexington, Kentucky 40536

Manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, is necessary for survival of aerobic life. Previously, we demonstrated that a Sp1-based promoter is essential for constitutive transcription and a NF-B-based intronic enhancer is responsible for cytokine-mediated induction. Here we show that nucleophosmin (NPM), a RNA-binding protein, binds to an 11G single-stranded loop in the promoter region and serves to integrate the Sp1 and NF-B responses. Disruption of the loop structure causes a reduction of both constitutive and inductive transcription due to loss of the binding motif for NPM. Interaction of NF-B·NPM·Sp1 facilitated by binding of NPM to the loop structure in the promoter region appears to comprise the basic complex for the transcriptional stimulation. These results suggest a novel molecular mechanism for communication between the enhancer and the GC-rich promoter.

Received for publication, September 20, 2006 , and in revised form, April 3, 2007.

^* The work was supported by National Institutes of Health Grants CA 49797 and CA 73599 (to D. K. S. C.). 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.

¹ To whom correspondence should be addressed: Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536-0305. Tel.: 859-257-3956; Fax: 859-323-1059; E-mail: dstcl00{at}uky.edu.

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

This article has been cited by other articles:

				Y. Xu, F. Fang, S. K. Dhar, A. Bosch, W. H. St. Clair, E. J. Kasarskis, and D. K. St. Clair Mutations in the SOD2 Promoter Reveal a Molecular Basis for an Activating Protein 2-Dependent Dysregulation of Manganese Superoxide Dismutase Expression in Cancer Cells Mol. Cancer Res., December 1, 2008; 6(12): 1881 - 1893. [Abstract] [Full Text] [PDF]