E3 ligase Cul2 mediates Drosophila early germ cell differentiation through targeting Bam
E3 ligase Cul2 mediates Drosophila early germ cell differentiation through targeting Bam
复制标题
E3连接酶Cul2通过靶向Bam介导果蝇早期生殖细胞分化
DOI：
10.1016/j.ydbio.2022.11.005
复制
发表时间：
2022-11-25
影响因子：
2.7
通讯作者：
Ji, Shanming
中科院分区：
文献类型：
--
作者：
Cai, Qingshuang;Yan, Jing;Ji, Shanming
果蝇卵巢是研究干细胞命运决定的体内调控机制最成熟和最优秀的系统之一。众所周知，由龛细胞释放的骨形态发生蛋白（BMP）信号通过抑制编码GSC分化的关键因子的大理石袋（bag-of-marbles，bam）基因的转录来促进生殖系干细胞（GSC）的维持。然而，Bam是否在翻译后水平上受到调控仍然是未知的。在这里，我们表明，E3连接酶Cullin-2（Cul 2）参与调节BAM泛素化，这可能发生在多个赖氨酸残基的BAM的C-末端区域。遗传学证据进一步支持Cul 2介导的BAM泛素化和营业额对于GSC维持和适当的种系发育至关重要的观点。总的来说，我们的数据不仅揭示了一种新的调控机制，通过这种机制，Bam在翻译后水平上受到控制，而且还为Cullin家族蛋白如何决定早期生殖细胞的分化命运提供了新的见解。
Drosophila ovary has been one of the most mature and excellent systems for studying the in vivo regulatory mechanisms of stem cell fate determination. It has been well-known that the bone morphogenetic protein (BMP) signaling released by the niche cells promotes the maintenance of germline stem cells (GSCs) through inhibiting the transcription of the bag-of-marbles (bam) gene, which encodes a key factor for GSC differentiation. However, whether Bam is regulated at the post-translational level remains largely unknown. Here we show that the E3 ligase Cullin-2 (Cul2) is involved in modulating Bam ubiquitination, which occurs probably at multiple lysine residues of Bam's C-terminal region. Genetic evidence further supports the notion that Cul2-mediated Bam ubiquitination and turnover are essential for GSC maintenance and proper germline development. Collectively, our data not only uncovers a novel regulatory mechanism by which Bam is controlled at the post-translational level, but also provides new insights into how Cullin family protein determines the differentiation fate of early germ cells.