A novel F-box protein is required for caspase activation during cellular remodeling in Drosophila
A novel F-box protein is required for caspase activation during cellular remodeling in Drosophila
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DOI：
10.1242/dev.050088
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发表时间：
2010-05-15
期刊：
影响因子：
4.6
通讯作者：
Steller, Hermann
中科院分区：
文献类型：
--
作者：
Bader, Maya;Arama, Eli;Steller, Hermann
果蝇和哺乳动物雄性生殖细胞的终末分化需要广泛的细胞结构重塑，许多细胞器的消除，以及细胞体积的大幅减少。相关的过程，被称为精子细胞的个体化，是由细胞凋亡机制，包括半胱天冬酶促进，但不会导致细胞死亡。从这个系统中的半胱天冬酶激活缺陷的基因筛选，我们分离出一种新的F-盒蛋白，我们称之为胡桃夹子，这是严格要求的半胱天冬酶激活和精子分化。胡桃夹子通过其F-box结构域与基于Cullin-1的泛素连接酶复合物（SCF）的成员：Cullin-1和SkpA相互作用。这种泛素连接酶不调节半胱天冬酶抑制剂DIAP 1和DIAP 2的稳定性，但物理结合布鲁斯，一种参与细胞凋亡调节的含BIR的巨大蛋白。此外，胡桃夹子突变体破坏蛋白酶体活性而不影响其分布。这些发现定义了一个新的SCF复合物所需的半胱天冬酶激活精子分化过程中，并强调在这一过程中调节蛋白水解的作用。
Terminal differentiation of male germ cells in Drosophila and mammals requires extensive cytoarchitectural remodeling, the elimination of many organelles, and a large reduction in cell volume. The associated process, termed spermatid individualization, is facilitated by the apoptotic machinery, including caspases, but does not result in cell death. From a screen for genes defective in caspase activation in this system, we isolated a novel F-box protein, which we termed Nutcracker, that is strictly required for caspase activation and sperm differentiation. Nutcracker interacts through its F-box domain with members of a Cullin-1-based ubiquitin ligase complex (SCF): Cullin-1 and SkpA. This ubiquitin ligase does not regulate the stability of the caspase inhibitors DIAP1 and DIAP2, but physically binds Bruce, a BIR-containing giant protein involved in apoptosis regulation. Furthermore, nutcracker mutants disrupt proteasome activity without affecting their distribution. These findings define a new SCF complex required for caspase activation during sperm differentiation and highlight the role of regulated proteolysis during this process.