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DOI10.1126/science.aan0218
UBE2O remodels the proteome during terminal erythroid differentiation
Nguyen A.T.; Prado M.A.; Schmidt P.J.; Sendamarai A.K.; Wilson-Grady J.T.; Min M.; Campagna D.R.; Tian G.; Shi Y.; Dederer V.; Kawan M.; Kuehnle N.; Paulo J.A.; Yao Y.; Weiss M.J.; Justice M.J.; Gygi S.P.; Fleming M.D.; Finley D.
发表日期2017
ISSN0036-8075
卷号357期号:6350
英文摘要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. © 2017, American Association for the Advancement of Science. All rights reserved.
英文关键词globin; proteasome; proteome; ribosome protein; ube 2o protein; ubiquitin conjugating enzyme; unclassified drug; hemoglobin beta chain; proteasome; proteome; ribosome protein; Ube2o protein, mouse; ubiquitin conjugating enzyme; anemia; enzyme; enzyme activity; gene; genetic analysis; genetic differentiation; mutation; rodent; Article; cell differentiation; cytosol; erythrocyte; erythroid cell; erythropoiesis; human; mutation; nonhuman; priority journal; protein degradation; proteomics; reticulocyte; ubiquitination; anemia; animal; C57BL mouse; cytology; enzymology; erythrocyte; genetics; HEK293 cell line; iron deficiency anemia; metabolism; mouse; mutant mouse strain; physiology; proteomics; ribosome; ubiquitination; Murinae; Anemia; Anemia, Hypochromic; Animals; beta-Globins; Erythrocytes; Erythroid Cells; Erythropoiesis; HEK293 Cells; Humans; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; Proteasome Endopeptidase Complex; Proteome; Proteomics; Reticulocytes; Ribosomal Proteins; Ribosomes; Ubiquitin-Conjugating Enzymes; Ubiquitination
语种英语
来源期刊Science
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/244875
作者单位Department of Cell Biology, Harvard Medical School, Boston, MA 02115, United States; Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, United States; Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN 38105, United States; Genetics and Genome Biology Program, Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, ON M5G 0A4, Canada; Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, United States; Department of Molecular and Clinical Pharmacology, University of California, Los Angeles, CA 90095, United States; Zentrum für Molekulare Biologie, Universität Heidelberg, Heidelberg, 69120, Germany
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Nguyen A.T.,Prado M.A.,Schmidt P.J.,et al. UBE2O remodels the proteome during terminal erythroid differentiation[J],2017,357(6350).
APA Nguyen A.T..,Prado M.A..,Schmidt P.J..,Sendamarai A.K..,Wilson-Grady J.T..,...&Finley D..(2017).UBE2O remodels the proteome during terminal erythroid differentiation.Science,357(6350).
MLA Nguyen A.T.,et al."UBE2O remodels the proteome during terminal erythroid differentiation".Science 357.6350(2017).
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