Cleavage and cytoplasmic relocalization of histone deacetylase 3 are important for apoptosis progression.
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 co-repressor 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.
Escaffit
Fabrice
F
Laboratoire de Biologie Moléculaire Eucaryote, UMR5099, CNRS and Université Paul Sabatier, IFR109, 118 Route de Narbonne, 31062 Toulouse Cedex 4, France.
Vaute
Olivier
O
Chevillard-Briet
Martine
M
Segui
Bruno
B
Takami
Yasunari
Y
Nakayama
Tatsuo
T
Trouche
Didier
D
D000107:Acetylation; D021581:Active Transport, Cell Nucleus; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D021381:Protein Transport; D015533:Transcriptional Activation; D019014:fas Receptor / Q000378:metabolism; D000099186:Histone Deacetylase 3
D020169:Caspases; D006655:Histone Deacetylases; D006657:Histones; D019014:fas Receptor; D000099186:Histone Deacetylase 3