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J. Biol. Chem., Vol. 282, Issue 7, 4504-4515, February 16, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/7/4504    most recent M608849200v1 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 Google Scholar Google Scholar Articles by Fries, B. Articles by Chemnitz, J. Search for Related Content PubMed PubMed Citation Articles by Fries, B. Articles by Chemnitz, J. Social Bookmarking                      What's this?

Analysis of Nucleocytoplasmic Trafficking of the HuR Ligand APRIL and Its Influence on CD83 Expression^*

Barbara Fries, Jochen Heukeshoven, Ilona Hauber, Cordula Grüttner, Carol Stocking, Ralph H. Kehlenbach, Joachim Hauber, and Jan Chemnitz¹

From the Heinrich-Pette-Institute for Experimental Virology and Immunology, Martinistrasse 52, 20251 Hamburg, Germany and the Zentrum für Biochemie und Molekulare Zellbiologie, Universität Göttingen, Humboldtallee 23, 37073 Göttingen, Germany

Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system and are able to sensitize even naïve T cells. Mature DC are characterized by expression of CD83, a surface molecule that is proposed to be involved in efficient T cell activation. It has been recently shown that CD83 mRNA is transported from the nucleus to the cytoplasm in a HuR- and CRM1-dependent manner. Therefore we here investigated the impact of two known protein ligands of HuR, pp32 and APRIL, on CD83 expression. Both pp32 (ANP32A) and APRIL (ANP32B) are shuttle proteins, and it has been reported earlier that these HuR ligands can act as adaptors that link HuR and the CRM1-specific nuclear export pathway. By employing RNA interference (RNAi) technology we demonstrate that pp32 is dispensable for CD83 expression, whereas APRIL contributes to the nuclear export and subsequent translation of CD83 mRNA. Furthermore, we have determined the nuclear import signal (NLS) as well as the nuclear export signal (NES) of human APRIL. Moreover, we analyzed the status of phosphorylation of endogenous APRIL and identified threonine 244 to be an as yet unrecognized phosphate acceptor. Finally, we were able to show that phosphorylation of this specific amino acid residue regulates the nuclear export of APRIL. In sum, we report here the signal sequences in APRIL that mediate its intracellular trafficking and provide evidence that this protein ligand of HuR is an important player in the post-transcriptional regulation of CD83 expression by affecting the nucleocytoplasmic translocation of CD83 mRNA.

Received for publication, September 14, 2006 , and in revised form, November 29, 2006.

^* This work was supported by Wilhelm Sander-Stiftung Grant 2003.033.1. 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.

This author is now deceased.

¹ To whom correspondence should be addressed: Heinrich-Pette-Institute for Experimental Virology and Immunology, Martinistrasse 52, 20251 Hamburg, Germany. Tel.: 49-40-48051-244; Fax: 49-40-48051-184; E-mail: jan.chemnitz{at}hpi.uni-hamburg.de.

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