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Originally published In Press as doi:10.1074/jbc.M201377200 on February 20, 2002

J. Biol. Chem., Vol. 277, Issue 18, 16139-16146, May 3, 2002
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AUF1 Is a bcl-2 A + U-rich Element-binding Protein Involved in bcl-2 mRNA Destabilization during Apoptosis*

Andrea LapucciDagger §, Martino DonniniDagger §, Laura PapucciDagger , Ewa WitortDagger , Alessio TempestiniDagger , Anna Bevilacqua||, Angelo Nicolin||, Gary Brewer**, Nicola SchiavoneDagger Dagger Dagger , and Sergio CapaccioliDagger Dagger Dagger

From the Dagger  Department of Experimental Pathology and Oncology, School of Medicine, University of Florence, 50134 Florence, Italy, || Department of Pharmacology, School of Medicine, University of Milan, 20129 Milan, Italy, and ** Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

We previously identified a conserved A + U-rich element (ARE) in the 3'-untranslated region of bcl-2 mRNA. We have also recently demonstrated that the bcl-2 ARE interacts with a number of ARE-binding proteins (AUBPs) whose pattern changes during apoptosis in association with bcl-2 mRNA half-life reduction. Here we show that the AUBP AUF1 binds in vitro to bcl-2 mRNA. The results obtained in a yeast RNA three-hybrid system have demonstrated that the 1-257-amino acid portion of p37 AUF1 (conserved in all isoforms), containing the two RNA recognition motifs, also binds to the bcl-2 ARE in vivo. UVC irradiation-induced apoptosis results in an increase of AUF1. Inhibition of apoptosis by a general caspase inhibitor reduces this increase by 2-3-fold. These results indicate involvement of AUF1 in the ARE/AUBP-mediated modulation of bcl-2 mRNA decay during apoptosis.

* This work was supported by grants from the Associazione Italiana Ricerca sul Cancro, Ministero dell'Università e Ricerca Scientifica e Tecnologica, and Ente Cassa di Risparmio di Firenze (to S. C.) and National Institutes of Health Grant CA 52443 (to G. B.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Both authors contributed equally to this work.

Recipient of a fellowship from the Federazione Italiana Ricerca Cancro.

Dagger Dagger To whom correspondence may be addressed: Dept. of Experimental Pathology and Oncology, School of Medicine, University of Florence, Viale G.B. Morgagni 50, 50134 Florence, Italy. Tel.: 390-55-4282309; Fax: 390-55-4282333; E-mail: sergio@unifi.it (S. C.) or nicola{at}unifi.it (N. S.).

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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