泛素（Ubiquitin）是一种存在于大多数真核细胞中的小蛋白。泛素依赖的蛋白质降解过程是真核生物细胞内的一种重要生理过程。此过程调控许多重要的生物学功能，如细胞的生长、分化、凋亡、信号转导、细胞周期运转、炎症反应和抗原呈递等。泛素化过程如发生错误会导致癌症诱发、遗传疾病等。
中科院动物研究所陈大华实验室的工作人员以果蝇生殖干细胞为研究对象，发现泛素化过程相关的一种重要的基因effete——编码一种泛素接合酶E2（Ubiquitin-conjugating Enzyme），在调控果蝇卵巢生殖干细胞的命运决定中发挥重要作用。进一步运用遗传学、生化及分子生物学等多种手段研究发现，Eff蛋白通过结合有丝分裂后期促进因子APC（一种多亚基的泛素连接酶E3）复合体中的dAPC2，介导细胞周期蛋白——Cyclin A的泛素化，从而通过调控Cyclin A蛋白水平的变化来影响生殖干细胞的命运。
该工作将泛素化信号通路调控与干细胞的命运决定联系起来，同时也表明了细胞周期调控因子直接控制干细胞的维持与分化。泛素化机理和细胞周期调控机制从酵母到高等哺乳动物高度保守，本研究工作暗示了哺乳动物中可能存在相似的调控机制控制干细胞的命运。该工作得到科技部、基金委以及中国科学院的支持。（生物谷Bioon.com）
生物谷推荐原始出处：
Development 11 Nov 2009 doi: 10.1242/dev.039032
Effete-mediated degradation of Cyclin A is essential for the maintenance of germline stem cells in Drosophila
Dongsheng Chen, Qi Wang, Haidong Huang, Laixin Xia, Xiaoyong Jiang, Lijuan Kan, Qinmiao Sun, and Dahua Chen*
Increasing evidence supports the idea that the regulation of stem cells requires both extrinsic and intrinsic mechanisms. However, much less is known about how intrinsic signals regulate the fate of stem cells. Studies on germline stem cells (GSCs) in the Drosophila ovary have provided novel insights into the regulatory mechanisms of stem cell maintenance. In this study, we demonstrate that a ubiquitin-dependent pathway mediated by the Drosophila eff gene, which encodes the E2 ubiquitin-conjugating enzyme Effete (Eff), plays an essential role in GSC maintenance. We show that Eff both physically and genetically interacts with dAPC2, a key component of the anaphase-promoting complex (APC), which acts as a multisubunit E3 ligase and plays an essential role in targeting mitotic regulators for degradation during exit from mitosis. This interaction indicates that Eff regulates the APC/C-mediated proteolysis pathway in GSCs. Moreover, we show that expression of a stable form of Cyclin A, but not full-length Cyclin A, results in GSC loss. Finally we show that, in common with APC2, Eff is required for the ubiquitylation of Cyclin A, and overexpression of full-length Cyclin A accelerates the loss of GSCs in the eff mutant background. Collectively, our data support the idea that Effete/APC-mediated degradation of Cyclin A is essential for the maintenance of germline stem cells in Drosophila. Given that the regulation of mitotic Cyclins is evolutionarily conserved between flies and mammals, our study also implies that a similar mechanism may be conserved in mammals.
