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

J. Biol. Chem., Vol. 283, Issue 29, 20037-20044, July 18, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/29/20037    most recent M710434200v2 M710434200v1 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 Moulton, V. R. Articles by Tsokos, G. C. Search for Related Content PubMed PubMed Citation Articles by Moulton, V. R. Articles by Tsokos, G. C. Social Bookmarking                      What's this?

The RNA-stabilizing Protein HuR Regulates the Expression of Chain of the Human T Cell Receptor-associated CD3 Complex^*

Vaishali R. Moulton, Vasileios C. Kyttaris, Yuang-Taung Juang, Bhabadeb Chowdhury, and George C. Tsokos¹

From the Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115 and Laboratory of Molecular Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892

T cell dysfunction is crucial to the pathogenesis of systemic lupus erythematosus (SLE); however, the molecular mechanisms involved in the deficient expression of the T cell receptor-associated CD3 chain in SLE are not clear. SLE T cells express abnormally increased levels of an alternatively spliced isoform of CD3 that lacks a 562-bp region in its 3'-untranslated region (UTR). We showed previously that two adenosine/uridine-rich elements (ARE) in this splice-deleted region of CD3 transcript are critical for the mRNA stability and protein expression of CD3. In this study we show for the first time that the mRNA-stabilizing protein HuR binds to these two ARE bearing regions of CD3 3'-UTR. Knockdown of HuR resulted in decreased expression of the CD3 chain, whereas overexpression led to the increase of CD3 chain levels. Additionally, overexpression of HuR in human T cells resulted in increased mRNA stability of CD3. Our results identify the 3'-UTR of CD3 as a novel target for the mRNA-stabilizing protein HuR. Thus, the absence of two critical AREs in the alternatively spliced CD3 3'-UTR found in SLE T cells may result in decreased HuR binding, representing a possible molecular mechanism contributing to the reduced stability and expression of CD3 in SLE.

Received for publication, December 21, 2007 , and in revised form, May 26, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grant RO1 AI42269. 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: 330 Brookline Ave., E/CLS 937, Boston, MA 02115. Tel.: 617-667-0751; Fax: 617-975-5299; E-mail: gtsokos{at}bidmc.harvard.edu.

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

This article has been cited by other articles:

				O. Papadaki, S. Milatos, S. Grammenoudi, N. Mukherjee, J. D. Keene, and D. L. Kontoyiannis Control of Thymic T Cell Maturation, Deletion and Egress by the RNA-Binding Protein HuR J. Immunol., June 1, 2009; 182(11): 6779 - 6788. [Abstract] [Full Text] [PDF]