HDAC4 stabilizes SIRT1 via sumoylation SIRT1 to delay cellular senescence
HDAC4 stabilizes SIRT1 via sumoylation SIRT1 to delay cellular senescence
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HDAC4 通过苏酰化 SIRT1 稳定 SIRT1，从而延缓细胞衰老。
DOI：
10.1111/1440-1681.12496
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发表时间：
2016-01-01
影响因子：
2.9
通讯作者：
Han, Limin
中科院分区：
文献类型：
--
作者：
Han, Xiaolin;Niu, Jing;Han, Limin
烟酰胺腺嘌呤二核苷酸依赖性蛋白脱乙酰酶沉默信息调节因子 2 (Sir2) 可调节多种生物体的细胞寿命。组蛋白脱乙酰酶 4 (HDAC4) 属于 HDAC IIa 类；这类 HDAC 由蛋白质组成，这些蛋白质是控制多效性细胞功能的基因表达的重要调节因子。然而，HDAC4在细胞衰老中的作用仍不清楚。这项研究表明，HDAC4 和 Sirtuin 1（SIRT1；Sir2 的哺乳动物同源物）的表达模式在细胞衰老过程中呈正相关。此外，HDAC4的过度表达可延缓衰老，而HDAC4的敲除会导致人类成纤维细胞过早衰老。此外，研究表明，HDAC4 通过增强其 SUMO 化修饰水平来增加内源性 SIRT1 的表达，从而稳定其蛋白水平。因此，这项研究为调控细胞衰老提供了新的分子机制。
The nicotinamide adenine dinucleotide-dependent protein deacetylase silent information regulator 2 (Sir2) regulates cellular lifespan in several organisms. Histone deacetylase 4 (HDAC4) belongs to the class IIa group of HDACs; this class of HDACs is composed of proteins that are important regulators of gene expression that control pleiotropic cellular functions. However, the role of HDAC4 in cellular senescence is still unknown. This study shows that the expression patterns of HDAC4 and Sirtuin 1 (SIRT1; the mammalian homolog of Sir2) are positively correlated during cellular senescence. Moreover, the overexpression of HDAC4 delays senescence, whereas the knockdown of HDAC4 leads to premature senescence in human fibroblasts. Furthermore, it is demonstrated that HDAC4 increases endogenous SIRT1 expression by enhancing its sumoylation modification levels, thereby stabilizing its protein levels. This study, therefore, provides a new molecular mechanism for the regulation of cellular senescence.