The effect of proteasome inhibitors on mammalian erythroid terminal differentiation

Cheng-Yao Chen, Lynne Pajak, Judith Tamburlin, Diane Bofinger, Stephen T. Koury

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Objective: Murine erythroblasts infected with the anemia-inducing strain of Friend virus (FVA cells) terminally differentiate to the reticulocyte stage after 48 hours of culture in vitro in response to erythropoietin (EPO). The objective of this study was to determine the possible role of proteasome-mediated proteolysis during the terminal differentiation of FVA cells. Materials and Methods: The proteasome inhibitors MG132 and lactacystin were used to perturb the normal function of proteasomes during terminal differentiation. Effects of proteasome inhibitors on terminal differentiation were quantitated by evaluation of cellular morphology after benzidine staining and by Western blot analyses. Results: Treatment of EPO-stimulated FVA cells with lactacystin or MG132 at later periods of culture increased accumulations of nuclear and cytosolic ubiquitinated proteins and decreased nuclear extrusion to less than 40% of controls. Conclusion: Our results suggest that the proteasomal degradation of ubiquitinated proteins plays an important role in the enucleation of mammalian erythroblasts.

Original languageEnglish
Pages (from-to)634-639
Number of pages6
JournalExperimental Hematology
Issue number7
Publication statusPublished - 2002 Aug 12

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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