返回首页
当前位置: 主页>生物研究>干细胞>

动物所在生殖干细胞命运调控研究中取得进展

Update:2017-05-12From:动物研究所 Hot:

  

生殖细胞是生物体内唯一能够将遗传信息传递给下一代的细胞类型。生殖细胞发育调控的研究一直是发育生物学核心方向之一。生殖干细胞不对称分裂(自我更新和分化)导致的细胞命运决择是生殖细胞发育及其谱系稳态维持的关键环节。果蝇卵巢生殖干细胞为生殖干细胞命运决定的在体(in vivo)机制研究提供了一个理想的模型。

果蝇生殖干细胞不对称分裂受到一系列内源和外源因子的调控。其中,果蝇著名的bag of marbles(bam)基因所编码的Bam蛋白是生殖干细胞不对称分裂过程中分化命运决定的关键因子。过去30年来,有关bam基因的遗传、进化及其调控特征在领域内已被广泛研究,但其产物Bam蛋白的生化特性一直是一个谜。

中国科学院动物研究所陈大华和孙钦秒研究组研究发现Bam蛋白是一种泛素结合蛋白,并与去泛素化酶Otu形成功能性的复合物,调节细胞周期蛋白Cyclin A的泛素化水平,从而影响Cyclin A的蛋白稳定性。该研究于5月8日以Bam-dependent deubiquitinase complex can disrupt germline stem cell maintenance by targeting cyclin A 为题,在线发表于《美国科学院院刊》(PNAS)。该项研究得到了国家基金委、科技部和中科院先导专项的支持。

参考文献

Bam-dependent deubiquitinase complex can disrupt germ-line stem cell maintenance by targeting cyclin A

Bam-dependent deubiquitinase complex can disrupt germ-line stem cell maintenance by targeting cyclin A

文献检索:doi: 10.1073/pnas.1619188114

Drosophila germ-line stem cells (GSCs) provide an excellent model to study the regulatory mechanisms of stem cells in vivo. Bag of marbles (bam) has been demonstrated to be necessary and sufficient to promote GSC and cystoblast differentiation. Despite extensive investigation of its regulation and genetic functions, the biochemical nature of the Bam protein has been unknown. Here, we report that Bam is an ubiquitin-associated protein and controls the turnover of cyclin A (CycA). Mechanistically, we found that Bam associated with Otu to form a deubiquitinase complex that stabilized CycA by deubiquitination, thus providing a mechanism to explain how ectopic expression of Bam in GSCs promotes differentiation. Collectively, our findings not only identify a biochemical function of Bam, which contributes to GSC fate determination, but also emphasizes the critical role of proper expression of cyclin proteins mediated by both ubiquitination and deubiquitination pathways in balancing stem cell self-renewal and differentiation.

相关参考
------分隔线----------------------------
推荐内容
Ads
关注微信
Ads