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UBE2O remodels the proteome during terminal erythroid differentiation
Anthony T Nguyen1, Miguel A Prado1, Paul J Schmidt2
1Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|August 5, 2017
Summary
A mutation in the Ube2o gene causes anemia by impairing the elimination of old proteins during red blood cell development. UBE2O targets ribosomal proteins for degradation, remodeling the proteome.
Area of Science:
- Cellular Biology
- Biochemistry
- Hematology
Background:
- Erythrocytes undergo significant proteome remodeling during terminal differentiation.
- The mechanisms for programmed elimination of cytosolic proteins in reticulocytes are not well understood.
- The ubiquitin-conjugating enzyme UBE2O is induced during erythropoiesis.
Purpose of the Study:
- To investigate the role of UBE2O in erythroid differentiation and proteome remodeling.
- To elucidate the mechanisms by which UBE2O contributes to reticulocyte maturation.
Main Methods:
- Proteomic analysis of murine Ube2o mutants.
- Identification of UBE2O substrates.
- Assessment of ribosome elimination during erythropoiesis in Ube2o mutants.
Main Results:
- A mutation in the murine Ube2o gene leads to anemia.
- UBE2O acts as a broad-spectrum ubiquitinating enzyme, remodeling the erythroid proteome.
- Ribosome elimination, a key feature of reticulocyte differentiation, is defective in Ube2o mutants.
- UBE2O directly targets ribosomal proteins and other substrates for proteasomal degradation.
Conclusions:
- UBE2O is crucial for programmed elimination of cytosolic proteins during erythropoiesis.
- UBE2O-mediated ubiquitination drives the transition to a simplified proteome in reticulocytes.
- The induction of ubiquitinating factors like UBE2O is a key mechanism in reticulocyte differentiation.
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