Key Lab of Physiology, Biochemistry & Molecular Biology of Hebei Province, Hebei Normal University, Shijiazhuang 050024, China; State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China.
State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China.
Cell Signal. 2014 Mar;26(3):556-63. doi: 10.1016/j.cellsig.2013.11.026. Epub 2013 Dec 2.
Histone deacetylase 4 (HDAC4) is involved in the regulation of many fundamental cell processes such as proliferation, differentiation, and survival via the modification of their substrates or protein-protein interactions. In this study, we found that HDAC4 could be upregulated under ER stress. There exists a direct interaction between HDAC4 and activating transcription factor 4 (ATF4). In vitro, overexpression of HDAC4 caused the retention of ATF4 in cytoplasm and inhibition of ATF4 transcriptional activity. ER stress could promote cell apoptosis through the upregulation of ATF4 levels and its target genes such as CHOP and TRB3. This effect was exacerbated by downregulation of HDAC4 levels. These results demonstrated that HDAC4 played an important role in the regulation of ER stress-induced apoptosis through interacting with ATF4 and inhibiting its transcriptional activity.
组蛋白去乙酰化酶 4（HDAC4）通过修饰其底物或蛋白-蛋白相互作用，参与调节许多基本的细胞过程，如增殖、分化和存活。在这项研究中，我们发现 ER 应激可使 HDAC4 上调。HDAC4 与激活转录因子 4（ATF4）之间存在直接相互作用。在体外，HDAC4 的过表达导致 ATF4 滞留在细胞质中并抑制 ATF4 的转录活性。ER 应激可通过上调 ATF4 水平及其靶基因（如 CHOP 和 TRB3）促进细胞凋亡。下调 HDAC4 水平会加剧这种效应。这些结果表明，HDAC4 通过与 ATF4 相互作用并抑制其转录活性，在调节 ER 应激诱导的细胞凋亡中发挥重要作用。
