Histone acetyltransferase PCAF up-regulated cell apoptosis in hepatocellular carcinoma via acetylating histone H4 and inactivating AKT signaling.
Histone acetyltransferase PCAF up-regulated cell apoptosis in hepatocellular carcinoma via acetylating histone H4 and inactivating AKT signaling.
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组蛋白乙酰转移酶 PCAF 通过乙酰化组蛋白 H4 和灭活 AKT 信号传导上调肝细胞癌中的细胞凋亡
DOI：
10.1186/1476-4598-12-96
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发表时间：
2013-08-27
期刊：
影响因子：
37.3
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Zheng X;Gai X;Ding F;Lu Z;Tu K;Yao Y;Liu Q
研究背景PCAF是一种重要的内源性组蛋白乙酰转移酶。本研究试图建立PCAF对HCC细胞凋亡的影响。方法采用IHC、DAPI染色、Caspase 3/7活性测定、BrdU测定、MTT测定、Western免疫印迹和免疫共沉淀等体外和体内实验。结果发现PCAF在大多数HCC细胞系中低水平表达。 PCAF 过表达可诱导 Huh7 和 HepG2 细胞中的细胞凋亡和生长停滞，并增加组蛋白 H4 乙酰化和 AKT 信号失活。通过沉默 Hep3B 细胞中的 PCAF 获得了相反的结果。免疫共沉淀实验证实Hep3B细胞核内PCAF蛋白与组蛋白H4蛋白结合。最后，体内实验证实了上述发现。结论这些数据表明PCAF通过乙酰化组蛋白H4和失活AKT信号传导促进细胞凋亡并起到HCC抑制因子的作用。
BackgroundPCAF is an important intrinsic histone acetyltransferases. This study tried to establish the effect of PCAF on HCC cell apoptosis.MethodBothin vitroandin vivoexperiments including IHC, DAPI staining, caspase 3/7 activity assay, BrdU assay, MTT assay, western immunoblotting and co-immunoprecipitation were used here.ResultsPCAF was found to be expressed at the low level in most of HCC cell lines. PCAF overexpression induced cell apoptosis and growth arrest with increased Histone H4 acetylation and inactivation of AKT signaling in Huh7 and HepG2 cells. The opposite results were obtained by silencing PCAF in Hep3B cells. The co-immunoprecipitation assay confirmed that PCAF protein was bound with histone H4 protein in the nucleus of Hep3B cells. Finally, thein vivoexperiment confirmed the findings mentioned-above.ConclusionThese data identified PCAF promotes cell apoptosis and functions as a HCC repressor through acetylating histone H4 and inactivating AKT signaling.
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