ArticleProceedings of the National Academy of Sciences of the United States of America1995
Erythropoietin-induced cellular differentiation requires prolongation of the G1 phase of the cell cycle.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 61 citations in OpenAlex.
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- Circular RNAs and Untranslated Regions in Acute Myeloid Leukemia.International journal of molecular sciences · 2023Review
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- PU.1 directly regulates cdk6 gene expression, linking the cell proliferation and differentiation programs in erythroid cells.The Journal of biological chemistry · 2010Article
- Temporal regulation of Stat5 activity in determination of cell differentiation program.Biochemical and biophysical research communications · 2007Article
- CDK2 catalytic activity and loss of nuclear tethering of retinoblastoma protein in childhood acute lymphoblastic leukemia.Leukemia · 2005Article
- Contrasting effects of basic fibroblast growth factor and neurotrophin 3 on cell cycle kinetics of mouse cortical stem cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2002Article
- The role of STATs in myeloid differentiation and leukemia.Oncogene · 2000Review
- JAK2 is required for induction of the murine DUB-1 gene.Molecular and cellular biology · 1997Article
- A proliferation switch for genetically modified cells.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- The murine DUB-1 gene is specifically induced by the betac subunit of interleukin-3 receptor.Molecular and cellular biology · 1996Article
- Erythropoietin-induced erythroid differentiation of the human erythroleukemia cell line TF-1 correlates with impaired STAT5 activation.The EMBO journal · 1996Article
- DUB-1, a deubiquitinating enzyme with growth-suppressing activity.Proceedings of the National Academy of Sciences of the United States of America · 1996Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Erythropoietin (EPO), like many other hematopoietic growth factors, can induce either growth or differentiation of hematopoietic cells. Little is known about the molecular basis of this cellular decision, in part because of a paucity of cell lines in which these two phenomena can be dissociated. Ectopic expression of the EPO receptor (EPO-R) in Ba/F3, a murine interleukin 3 (IL-3)-dependent progenitor cell line, confers EPO-dependent cell growth. In these cells (Ba/F3-EPO-R), EPO also induces beta-globin mRNA, a specific marker of erythroid differentiation. Here we show that the induction of erythroid differentiation by EPO requires a delay in cell growth and a prolongation of the (G1) phase of the cell cycle. Interestingly, this effect on G1 prolongation was concentration dependent. At low EPO concentrations (0.05-0.1 unit of EPO per ml; 1 pM EPO = 0.01 unit of EPO per ml), EPO prolonged G1 and induced differentiation; at high concentrations (0.5-10.0 units per ml), EPO shortened G1 and preferentially stimulated growth. IL-3 stimulated Ba/F3 growth but not differentiation at all growth factor concentrations ranging from 0.1 to 500 pM. Moreover, IL-3 suppressed EPO-induced beta-globin induction in a dose-dependent manner. This suppression correlated with the shortening of G1 by IL-3. Taken together, these data demonstrate distinct effects of EPO and IL-3 and a balance between erythroid growth and differentiation that is cell cycle dependent.
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