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Molecular and Cellular Biology, January 2007, p. 554-567, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.00869-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cleavage and Cytoplasmic Relocalization of Histone Deacetylase 3 Are Important for Apoptosis Progression{triangledown} ,{dagger}

Fabrice Escaffit,1 Olivier Vaute,1 Martine Chevillard-Briet,1 Bruno Segui,2 Yasunari Takami,3 Tatsuo Nakayama,3 and Didier Trouche1*

Laboratoire de Biologie Moléculaire Eucaryote, UMR5099, CNRS and Université Paul Sabatier, IFR109, 118 Route de Narbonne, 31062 Toulouse Cedex 4, France,1 Laboratoire de Biochimie, Régulations cellulaires, lipidoses et athérosclérose, INSERM U466, IFR31, CHU Rangueil, 1 avenue J. Poulhès, 31403 Toulouse Cedex 4, France,2 Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Miyazaki Medical College, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki 889-1692, Japan3

Received 16 May 2006/ Returned for modification 31 July 2006/ Accepted 30 October 2006

The apoptotic process is accompanied by major changes in chromatin structure and gene expression. The apoptotic genetic program is progressively set up with the inhibition of antiapoptotic genes and the activation of proapoptotic ones. Here, we show that the histone deacetylase 3 (HDAC-3), which is a known corepressor of many proapoptotic genes, is subjected to proteolytic cleavage during apoptosis in a cell type- and species-independent manner. This cleavage is caspase dependent and leads to the loss of the C-terminal part of HDAC-3. The cleaved form of HDAC-3 accumulates in the cytoplasm. Furthermore, we found that forced nuclear localization of HDAC-3 decreases the efficiency of apoptosis induction, indicating that HDAC-3 cytoplasmic relocalization is important for the apoptotic process. Finally, we observed that HDAC-3 cleavage allowed increased histone acetylation and transcriptional activation on a proapoptotic HDAC-3-target gene, the Fas-encoding gene. Altogether, our results thus indicate that HDAC-3 cleavage is crucial for efficient apoptosis induction because it allows the activation of some proapoptotic genes during apoptosis progression.

* Corresponding author. Mailing address: Laboratoire de Biologie Moléculaire Eucaryote, UMR5099, CNRS and Université Paul Sabatier, IFR109, 118 Route de Narbonne, 31062 Toulouse Cedex 4, France. Phone: 33 5 61 33 59 15. Fax: 33 5 61 33 58 86. E-mail: trouche{at}ibcg.biotoul.fr.

{triangledown} Published ahead of print on 13 November 2006.

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

Molecular and Cellular Biology, January 2007, p. 554-567, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.00869-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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