Center for Developmental Biology, School of Life Sciences, Anhui Agricultural University, Hefei, Anhui, China 230036.
State Key Laboratory of Membrane Biology, Chinese Academy of Sciences, Chaoyang District, Beijing, China 100101.
Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):6316-6321. doi: 10.1073/pnas.1619188114. Epub 2017 May 8.
germ-line stem cells (GSCs) provide an excellent model to study the regulatory mechanisms of stem cells in vivo. () 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.
生殖系干细胞 (GSCs) 为研究体内干细胞的调控机制提供了极好的模型。()已被证明是促进 GSC 和囊胚母细胞分化所必需和充分的。尽管对其调控和遗传功能进行了广泛的研究，但 Bam 蛋白的生化性质尚不清楚。在这里，我们报告 Bam 是一种与泛素相关的蛋白质，并控制细胞周期蛋白 A (CycA) 的周转。在机制上，我们发现 Bam 与 Otus 相关形成一个去泛素化酶复合物，通过去泛素化稳定 CycA，从而提供了一种机制来解释 Bam 在 GSCs 中的异位表达如何促进分化。总的来说，我们的发现不仅确定了 Bam 的生化功能，这有助于 GSC 命运的决定，而且强调了泛素化和去泛素化途径介导的 cyclin 蛋白的适当表达在平衡干细胞自我更新和分化中的关键作用。
