Protein Palmitoylation Regulates Neural Stem Cell Differentiation by Modulation of EID1 Activity
Protein Palmitoylation Regulates Neural Stem Cell Differentiation by Modulation of EID1 Activity
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DOI：
10.1007/s12035-015-9481-y
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发表时间：
2016-10-01
影响因子：
5.1
通讯作者：
Hao, Aijun
中科院分区：
文献类型：
--
作者：
Chen, Xueran;Du, Zhaoxia;Hao, Aijun
棕榈酰化在神经干细胞（NSCs）自我更新和分化之间的转换中的功能意义还没有很好地定义，并且蛋白质棕榈酰化的潜在机制还没有很好地理解。在此，小鼠NSC被用作模型系统，并且在蛋白质棕榈酰化抑制剂2-溴棕榈酸酯（2BRO）的存在下监测细胞行为。我们的数据表明，2BRO损害神经干细胞分化为神经元和胶质细胞和受损的NSC细胞周期退出。此外，结果表明棕榈酰化修饰的E1 A样分化抑制因子1（EID 1），这种修饰调节EID 1降解和CREB结合蛋白（CBP）/p300组蛋白乙酰转移酶活性在神经干细胞自我更新和分化之间的转换。我们的研究结果扩展了棕榈酰化的细胞作用，表明它在乙酰化依赖的基因表达网络中充当调节剂，并建立了棕榈酰化在神经干细胞多能性维持和分化之间的转换中的表观遗传调节功能。
The functional significance of palmitoylation in the switch between self-renewal and differentiation of neural stem cells (NSCs) is not well defined, and the underlying mechanisms of protein palmitoylation are not well understood. Here, mouse NSCs were used as a model system and cell behavior was monitored in the presence of the protein palmitoylation inhibitor 2-bromopalmitate (2BRO). Our data show that 2BRO impaired the differentiation of NSCs into both neurons and glia and impaired NSC cell cycle exit. Moreover, the results show that palmitoylation modified E1A-like inhibitor of differentiation one (EID1) and this modification regulated EID1 degradation and CREB-binding protein (CBP)/p300 histone acetyltransferase activity at the switch between self-renewal and differentiation of NSCs. Our results extended the cellular role of palmitoylation, suggesting that it acts as a regulator in the acetylation-dependent gene expression network, and established the epigenetic regulatory function of palmitoylation in the switch between maintenance of multipotency and differentiation in NSCs.