泛素（Ubiquitin）是一種存在于大多數(shù)真核細(xì)胞中的小蛋白。泛素依賴的蛋白質(zhì)降解過程是真核生物細(xì)胞內(nèi)的一種重要生理過程。此過程調(diào)控許多重要的生物學(xué)功能,，如細(xì)胞的生長,、分化,、凋亡,、信號轉(zhuǎn)導(dǎo)、細(xì)胞周期運(yùn)轉(zhuǎn),、炎癥反應(yīng)和抗原呈遞等,。泛素化過程如發(fā)生錯(cuò)誤會(huì)導(dǎo)致癌癥誘發(fā)、遺傳疾病等,。
中科院動(dòng)物研究所陳大華實(shí)驗(yàn)室的工作人員以果蠅生殖干細(xì)胞為研究對象,，發(fā)現(xiàn)泛素化過程相關(guān)的一種重要的基因effete——編碼一種泛素接合酶E2（Ubiquitin-conjugating Enzyme），在調(diào)控果蠅卵巢生殖干細(xì)胞的命運(yùn)決定中發(fā)揮重要作用,。進(jìn)一步運(yùn)用遺傳學(xué),、生化及分子生物學(xué)等多種手段研究發(fā)現(xiàn)，Eff蛋白通過結(jié)合有絲分裂后期促進(jìn)因子APC（一種多亞基的泛素連接酶E3）復(fù)合體中的dAPC2,，介導(dǎo)細(xì)胞周期蛋白——Cyclin A的泛素化,，從而通過調(diào)控Cyclin A蛋白水平的變化來影響生殖干細(xì)胞的命運(yùn)。
該工作將泛素化信號通路調(diào)控與干細(xì)胞的命運(yùn)決定聯(lián)系起來,，同時(shí)也表明了細(xì)胞周期調(diào)控因子直接控制干細(xì)胞的維持與分化,。泛素化機(jī)理和細(xì)胞周期調(diào)控機(jī)制從酵母到高等哺乳動(dòng)物高度保守，本研究工作暗示了哺乳動(dòng)物中可能存在相似的調(diào)控機(jī)制控制干細(xì)胞的命運(yùn),。該工作得到科技部,、基金委以及中國科學(xué)院的支持。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
