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Molecular and Cellular Biology, June 2006, p. 4746-4757, Vol. 26, No. 12
0270-7306/06/$08.00+0     doi:10.1128/MCB.00959-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Repression of the Antiapoptotic Molecule Galectin-3 by Homeodomain-Interacting Protein Kinase 2-Activated p53 Is Required for p53-Induced Apoptosis{dagger}

Barbara Cecchinelli,1 Luca Lavra,2,6 Cinzia Rinaldo,1 Stefano Iacovelli,1 Aymone Gurtner,1 Alessandra Gasbarri,3 Alessandra Ulivieri,2,6 Fabrizio Del Prete,3 Maria Trovato,4 Giulia Piaggio,1 Armando Bartolazzi,3,5* Silvia Soddu,1* and Salvatore Sciacchitano2,6,7*

Department of Experimental Oncology, Regina Elena Cancer Institute, 00158 Rome, Italy,1 S. Pietro Fatebenefratelli Hospital-Associazione Fatebenefratelli per la Ricerca, 00189 Rome, Italy,2 Department of Pathology, Sant'Andrea Hospital, 00189 Rome, Italy,3 Department of Human Pathology, University of Messina, 98100 Messina, Italy,4 Cellular and Molecular Tumor Pathology Laboratory, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden,5 Department of Experimental Medicine and Pathology, II Faculty of Medicine, University "La Sapienza,",6 Institute of Neurobiology, Experimental and Molecular Medicine, Centro Nazionale Ricerche, Rome, Italy7

Received 24 May 2005/ Returned for modification 9 July 2005/ Accepted 17 March 2006

Galectin 3 (Gal-3), a member of the ß-galactoside binding lectin family, exhibits antiapoptotic functions, and its aberrant expression is involved in various aspects of tumor progression. Here we show that p53-induced apoptosis is associated with transcriptional repression of Gal-3. Previously, it has been reported that phosphorylation of p53 at Ser46 is important for transcription of proapoptotic genes and induction of apoptosis and that homeodomain-interacting protein kinase 2 (HIPK2) is specifically involved in these functions. We show that HIPK2 cooperates with p53 in Gal-3 repression and that this cooperation requires HIPK2 kinase activity. Gene-specific RNA interference demonstrates that HIPK2 is essential for repression of Gal-3 upon induction of p53-dependent apoptosis. Furthermore, expression of a nonrepressible Gal-3 prevents HIPK2- and p53-induced apoptosis. These results reveal a new apoptotic pathway induced by HIPK2-activated p53 and requiring repression of the antiapoptotic factor Gal-3.

* Corresponding author. Mailing address for Armando Bartolazzi: Sant'Andrea Hospital, Via di Grottarossa 1035, 00189 Rome, Italy. Phone and fax: 39 06 8034 5321. E-mail: Armando.Bartolazzi{at}cck.ki.se. Mailing address for Silvia Soddu: Regina Elena Cancer Institute, Via delle Messi d'Oro 156, Rome, Italy. Phone: 39 06 5266 2563. Fax: 39 06 5266 2505. E-mail: soddu{at}ifo.it. Mailing address for Salvatore Sciacchitano: S. Pietro Fatebenefratelli Hospital, Via Cassia 600, 00189 Rome, Italy. Phone: 39 06 3358 2878. Fax: 39 06 3325 1278. E-mail: salvatore.sciacchitano{at}uniroma1.it.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, June 2006, p. 4746-4757, Vol. 26, No. 12
0270-7306/06/$08.00+0     doi:10.1128/MCB.00959-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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