UBE2O remodels the proteome during terminal erythroid differentiation

Science. 2017 Aug 4;357(6350):eaan0218. 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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / genetics
  • Anemia, Hypochromic / genetics
  • Animals
  • Erythrocytes / cytology
  • Erythrocytes / enzymology
  • Erythroid Cells / cytology*
  • Erythroid Cells / enzymology
  • Erythropoiesis / genetics
  • Erythropoiesis / physiology*
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutation
  • Proteasome Endopeptidase Complex / metabolism
  • Proteome / metabolism
  • Proteomics
  • Reticulocytes / cytology
  • Reticulocytes / enzymology
  • Ribosomal Proteins / metabolism*
  • Ribosomes / metabolism
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism*
  • Ubiquitination*
  • beta-Globins / genetics
  • beta-Globins / metabolism


  • Proteome
  • Ribosomal Proteins
  • beta-Globins
  • Ube2o protein, mouse
  • Ubiquitin-Conjugating Enzymes
  • Proteasome Endopeptidase Complex