UBE2O remodels the proteome during terminal erythroid differentiation.
Anthony T NguyenMiguel A PradoPaul J SchmidtAnoop K SendamaraiJoshua T Wilson-GradyMingwei MinDean R CampagnaGeng TianYuan ShiVerena DedererMona KawanNathalie KühnleJoao A PauloYu YaoMitchell J WeissMonica J JusticeSteven P GygiMark Daniel FlemingDaniel FinleyPublished in: Science (New York, N.Y.) (2018)
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 Ube2o 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 Ube2o-/- 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.