组蛋白脱乙酰酶6脱乙酰催化域的底物蛋白及功能

Substrates of deacetylation catalytic domain and functions of histone deacetylase 6

蛋白质的乙酰化修饰是蛋白功能调节的重要机制,影响细胞增殖、迁移、凋亡等多方面功能。靶蛋白的乙酰化状态受组蛋白脱乙酰酶(histone deacety-lases,HDACs)和组蛋白乙酰转移酶(histone acetyl-transferases,HATs)的共同调节。乙酰化和脱乙酰化状态失衡可影响细胞正常的生命活动。

Histone deacetylase 6(HDAC6),one member of HDACs family,is regarded as an unusual HDAC due to its unique properties:mainly located in the cytoplasm,containing 2 independent deacetylase catalytic domains and a zinc finger ubiquitin-binding domain.All specific HDAC6 inhibitors have been shown to target deacetylase catalytic domains,regulating its deacetylation activity without effect on ubiquitin-binding domain.Currently,HDAC6 inhibitors are investigated for use in the treatment of many diseases such as malignancy,neurodegenerative disorders and cardiovascular diseases,indicating that deacetylation by HDAC6 plays an important role in the regulation of pathophysiological functions.HDAC6 has been demonstrated to deacetylate several substrates including tubulin,HSP90,cortactin,and so on.Here,we review the progress in the study of substrates for deacetylation by HDAC6 and their functions.