Nguyen Anthony T, Prado Miguel A, Schmidt Paul J, Sendamarai Anoop K, Wilson-Grady Joshua T, Min Mingwei, Campagna Dean R, Tian Geng, Shi Yuan, Dederer Verena, Kawan Mona, Kuehnle Nathalie, Paulo Joao A, Yao Yu, Weiss Mitchell J, Justice Monica J, Gygi Steven P, Fleming Mark D, Finley Daniel
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Science. 2017 Aug 4;357(6350). doi: 10.1126/science.aan0218.
During terminal differentiation, the global protein complement is remodeled, as epitomized by erythrocytes, whose cytosol is ~98% globin. The erythroid proteome undergoes a rapid transition at the reticulocyte stage; however, the mechanisms driving programmed elimination of preexisting cytosolic proteins are unclear. We found that a mutation in the murine gene, which encodes a ubiquitin-conjugating enzyme induced during erythropoiesis, results in anemia. Proteomic analysis suggested that UBE2O is a broad-spectrum ubiquitinating enzyme that remodels the erythroid proteome. In particular, ribosome elimination, a hallmark of reticulocyte differentiation, was defective in mutants. UBE2O recognized ribosomal proteins and other substrates directly, targeting them to proteasomes for degradation. Thus, in reticulocytes, the induction of ubiquitinating factors may drive the transition from a complex to a simple proteome.
在终末分化过程中，整体蛋白质组成会发生重塑，红细胞就是典型例子，其胞质溶胶约98%是珠蛋白。红系蛋白质组在网织红细胞阶段经历快速转变；然而，驱动对先前存在的胞质蛋白进行程序性清除的机制尚不清楚。我们发现，小鼠基因发生突变，该基因编码一种在红细胞生成过程中诱导产生的泛素结合酶，会导致贫血。蛋白质组学分析表明，UBE2O是一种重塑红系蛋白质组的广谱泛素化酶。特别是，核糖体清除作为网织红细胞分化的一个标志，在突变体中存在缺陷。UBE2O直接识别核糖体蛋白和其他底物，将它们靶向蛋白酶体进行降解。因此，在网织红细胞中，泛素化因子的诱导可能驱动从复杂蛋白质组向简单蛋白质组的转变。
