UBE2O remodels the proteome during terminal erythroid differentiation
- 4 August 2017
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 357 (6350)
- https://doi.org/10.1126/science.aan0218
Abstract
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.Funding Information
- National Institutes of Health (award313215, R01 DK61692)
- National Heart, Lung, and Blood Institute (award302896, 5R21HL116210)
- National Heart, Lung, and Blood Institute (award302897, 5R01HL125710)
- National Heart, Lung, and Blood Institute (award302898, F30HL124980)
- Biogen (award313216)
- National Institute of Diabetes and Digestive and Kidney Diseases (award312802, R01 DK087992)
- Biogen Idec (award312803, NA)
- National Institute of Diabetes and Digestive and Kidney Diseases (award302900, 5K01DK098285)
- National Institute of General Medical Sciences (award302899, T32GM007753)
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