A Conserved F Box Regulatory Complex Controls Proteasome Activity in Drosophila
A Conserved F Box Regulatory Complex Controls Proteasome Activity in Drosophila
复制标题
DOI：
10.1016/j.cell.2011.03.021
复制
发表时间：
2011-04-29
期刊：
影响因子：
64.5
通讯作者：
Steller, Hermann
中科院分区：
文献类型：
--
作者：
Bader, Maya;Benjamin, Sigi;Steller, Hermann
泛素-蛋白酶体系统催化细胞内蛋白质的降解。尽管蛋白质的遍在化决定了其稳定性，但越来越多的证据表明蛋白酶体功能也受到调节。我们报告了一个保守的蛋白酶体调节复合物的功能特性。我们确定DmPI 31作为F盒蛋白胡桃夹子的结合伴侣，胡桃夹子是果蝇精子分化过程中caspase激活所需的SCF泛素连接酶（E3）的一个组成部分。DmPI 31通过哺乳动物FBXO 7和PI 31也使用的保守机制结合胡桃夹子。胡桃夹子促进DmPI 31的稳定性，这是半胱天冬酶激活，蛋白酶体功能和精子分化所必需的。DmPI 31可以在体外激活26 S蛋白酶体，并且增加DmPI 31水平抑制体内蛋白酶体活性降低引起的缺陷。此外，DmPI 31功能的丧失导致致死性、细胞周期异常和蛋白质降解缺陷，表明DmPI 31是正常蛋白酶体活性生理学上所需的。
The ubiquitin-proteasome system catalyzes the degradation of intracellular proteins. Although ubiquitination of proteins determines their stabilities, there is growing evidence that proteasome function is also regulated. We report the functional characterization of a conserved proteasomal regulatory complex. We identified DmPI31 as a binding partner of the F box protein Nutcracker, a component of an SCF ubiquitin ligase (E3) required for caspase activation during sperm differentiation in Drosophila. DmPI31 binds Nutcracker via a conserved mechanism that is also used by mammalian FBXO7 and PI31. Nutcracker promotes DmPI31 stability, which is necessary for caspase activation, proteasome function, and sperm differentiation. DmPI31 can activate 26S proteasomes in vitro, and increasing DmPI31 levels suppresses defects caused by diminished proteasome activity in vivo. Furthermore, loss of DmPI31 function causes lethality, cell-cycle abnormalities, and defects in protein degradation, demonstrating that DmPI31 is physiologically required for normal proteasome activity.