Gcn5 determines the fate of Drosophila germline stem cells through degradation of Cyclin A
Gcn5 determines the fate of Drosophila germline stem cells through degradation of Cyclin A
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Gcn5 通过降解 Cyclin A 决定果蝇生殖干细胞的命运
DOI：
10.1096/fj.201601217r
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发表时间：
2017-05-01
期刊：
影响因子：
4.8
通讯作者：
Xia, Laixin
中科院分区：
文献类型：
--
作者：
Liu, Tianqi;Wang, Qi;Xia, Laixin
波动的CDK-CYCLIN复合物在细胞周期控制中起着普遍的作用。许多类型的干细胞利用细胞周期的独特特征来促进不对称分裂。然而，这些特征建立的方式仍然知之甚少。果蝇雌性生殖系干细胞（Drosophila female germline stem cells, GSCs）的细胞周期具有短G(1)期和长G(2)期的特点，是研究干细胞命运决定中细胞周期控制的一个很好的模型。利用果蝇雌性GSCs模型，我们发现了Gcn5，这是第一个发现的组蛋白乙酰转移酶，可以维持果蝇卵巢中的种系干细胞。结果表明，Gcn5对于bam的转录沉默是必不可少的，但它与Cyclin A相互作用以促进GSCs中的适当周转。结果还表明Gcn5促进Cyclin A泛素化，这依赖于它的乙酰化活性。最后，结果表明，Cyclin A的敲低挽救了Gcn5缺失引起的GSC-loss表型。总的来说，这些发现支持Gcn5通过乙酰化促进Cyclin A泛素化和适当的周转，从而决定GSCs的命运的结论。-刘涛，王强，李，文，毛峰，岳，生，刘，生，刘，学，肖，生，夏，丽，Gcn5通过降解Cyclin A决定果蝇种系干细胞的命运。
The fluctuating CDK-CYCLIN complex plays a general role in cell-cycle control. Many types of stem cells use unique features of the cell cycle to facilitate asymmetric division. However, the manner in which these features are established remains poorly understood. The cell cycle of Drosophila female germline stem cells (GSCs) is characterized by short G(1) and very long G(2) phases, making it an excellent model for the study of cell cycle control in stem cell fate determination. Using a Drosophila female GSCs model, we found Gcn5, the first discovered histone acetyltransferase, to maintain germline stem cells in Drosophila ovaries. Results showed that Gcn5 is dispensable for the transcriptional silencing of bam, but interacts with Cyclin A to facilitate proper turnover in GSCs. Results also showed that Gcn5 promotes Cyclin A ubiquitination, which is dependent on its acetylating activity. Finally, results showed that knockdown of Cyclin A rescued the GSC-loss phenotype caused by lack of Gcn5. Collectively, these findings support the conclusion that Gcn5 acts through acetylation to facilitate Cyclin A ubiquitination and proper turnover, thereby determining the fate of GSCs.-Liu, T., Wang, Q., Li, W., Mao, F., Yue, S., Liu, S., Liu, X., Xiao, S., Xia, L. Gcn5 determines the fate of Drosophila germline stem cells through degradation of Cyclin A.