Cleavage and cytoplasmic relocalization of histone deacetylase 3 are important for apoptosis progression
Cleavage and cytoplasmic relocalization of histone deacetylase 3 are important for apoptosis progression
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DOI：
10.1128/mcb.00869-06
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发表时间：
2007-01-01
影响因子：
5.3
通讯作者：
Trouche, Didier
中科院分区：
文献类型：
--
作者：
Escaffit, Fabrice;Vaute, Olivier;Trouche, Didier
凋亡过程伴随着染色质结构和基因表达的重大变化。凋亡遗传程序是随着抗凋亡基因的抑制和促凋亡基因的激活而逐步建立起来的。在这里，我们发现组蛋白去乙酰化酶3 （HDAC-3）是许多促凋亡基因的已知协同抑制因子，在细胞凋亡过程中以细胞类型和物种无关的方式受到蛋白水解裂解。这种裂解是半胱天冬酶依赖的，导致HDAC-3的c端部分丢失。分裂形式的HDAC-3在细胞质中积累。此外，我们发现HDAC-3的强制核定位降低了诱导凋亡的效率，这表明HDAC-3的细胞质再定位在凋亡过程中很重要。最后，我们观察到HDAC-3的切割增加了促凋亡HDAC-3靶基因（fas编码基因）的组蛋白乙酰化和转录激活。总之，我们的研究结果表明，HDAC-3切割对于有效诱导细胞凋亡至关重要，因为它允许在细胞凋亡过程中激活一些促凋亡基因。
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.