This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tamir, A.
Right arrow Articles by Ben-David, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tamir, A.
Right arrow Articles by Ben-David, Y.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 1999, p. 4452-4464, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Fli-1, an Ets-Related Transcription Factor, Regulates Erythropoietin-Induced Erythroid Proliferation and Differentiation: Evidence for Direct Transcriptional Repression of the Rb Gene during Differentiation

Ami Tamir,1 Jeff Howard,1 Rachel R. Higgins,1 You-Jun Li,1 Lloyd Berger,1 Eldad Zacksenhaus,2 Marciano Reis,3 and Yaacov Ben-David1,*

Department of Medical Biophysics, Cancer Biology Research, Sunnybrook and Women's College Health Science Centre, University of Toronto, Toronto, Ontario M4N 3M5,1 Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M1,2 and Department of Laboratory Medicine and Pathophysiology, University of Toronto, Toronto, Ontario M4N 3M2,3 Canada

Received 10 September 1998/Returned for modification 4 December 1998/Accepted 11 March 1999

Erythropoietin (Epo) is a major regulator of erythropoiesis that alters the survival, proliferation, and differentiation of erythroid progenitor cells. The mechanism by which these events are regulated has not yet been determined. Using HB60, a newly established erythroblastic cell line, we show here that Epo-induced terminal erythroid differentiation is associated with a transient downregulation in the expression of the Ets-related transcription factor Fli-1. Constitutive expression of Fli-1 in HB60 cells, similar to retroviral insertional activation of Fli-1 observed in Friend murine leukemia virus (F-MuLV)-induced erythroleukemia, blocks Epo-induced differentiation while promoting Epo-induced proliferation. These results suggest that Fli-1 modulates the response of erythroid cells to Epo. To understand the mechanism by which Fli-1 regulates erythropoiesis, we searched for downstream target genes whose expression is regulated by this transcription factor. Here we show that the retinoblastoma (Rb) gene, which was previously shown to be involved in the development of mature erythrocytes, contains a Fli-1 consensus binding site within its promoter. Fli-1 binds to this cryptic Ets consensus site within the Rb promoter and transcriptionally represses Rb expression. Both the expression level and the phosphorylation status of Rb are consistent with the response of HB60 cells to Epo-induced terminal differentiation. We suggest that the negative regulation of Rb by Fli-1 could be one of the critical determinants in erythroid progenitor cell differentiation that is specifically deregulated during F-MuLV-induced erythroleukemia.

* Corresponding author. Mailing address: Department of Medical Biophysics, University of Toronto, Cancer Biology Research, Sunnybrook and Women's College Health Science Centre, 2075 Bayview Ave., S-Wing, Toronto, Ontario M4N 3M5, Canada. Phone: (416) 480-6100, ext. 3350. Fax: (416) 480-5703. E-mail: bendavid{at}srcl.sunnybrook.utoronto.ca.

Molecular and Cellular Biology, June 1999, p. 4452-4464, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Usenko, T., Li, Y.-J., Haeri, M., Li, Y., Vecchiarelli-Federico, L. M., Zhao, X., Prchal, J. T., Ben-David, Y. (2009). Enrichment of Sca1+ hematopoietic progenitors in polycythemic mice inhibits leukemogenesis. Blood 114: 1831-1841 [Abstract] [Full Text]  
  • Stankiewicz, M. J., Crispino, J. D. (2009). ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells. Blood 113: 3337-3347 [Abstract] [Full Text]  
  • Zhang, X. K., Moussa, O., LaRue, A., Bradshaw, S., Molano, I., Spyropoulos, D. D., Gilkeson, G. S., Watson, D. K. (2008). The Transcription Factor Fli-1 Modulates Marginal Zone and Follicular B Cell Development in Mice. J. Immunol. 181: 1644-1654 [Abstract] [Full Text]  
  • Bouilloux, F., Juban, G., Cohet, N., Buet, D., Guyot, B., Vainchenker, W., Louache, F., Morle, F. (2008). EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation. Blood 112: 576-584 [Abstract] [Full Text]  
  • Cui, J.-W., Li, Y.-J., Sarkar, A., Brown, J., Tan, Y.-H., Premyslova, M., Michaud, C., Iscove, N., Wang, G.-J., Ben-David, Y. (2007). Retroviral insertional activation of the Fli-3 locus in erythroleukemias encoding a cluster of microRNAs that convert Epo-induced differentiation to proliferation. Blood 110: 2631-2640 [Abstract] [Full Text]  
  • Cervi, D., Shaked, Y., Haeri, M., Usenko, T., Lee, C. R., Haigh, J. J., Nagy, A., Kerbel, R. S., Yefenof, E., Ben-David, Y. (2007). Enhanced natural-killer cell and erythropoietic activities in VEGF-A-overexpressing mice delay F-MuLV-induced erythroleukemia. Blood 109: 2139-2146 [Abstract] [Full Text]  
  • Agromayor, M., Wloga, E., Naglieri, B., Abrashkin, J., Verma, K., Yamasaki, L. (2006). Visualizing Dynamic E2F-Mediated Repression In Vivo. Mol. Cell. Biol. 26: 4448-4461 [Abstract] [Full Text]  
  • van den Akker, E., Ano, S., Shih, H.-M., Wang, L.-C., Pironin, M., Palvimo, J. J., Kotaja, N., Kirsh, O., Dejean, A., Ghysdael, J. (2005). FLI-1 Functionally Interacts with PIASx{alpha}, a Member of the PIAS E3 SUMO Ligase Family. J. Biol. Chem. 280: 38035-38046 [Abstract] [Full Text]  
  • Nishigaki, K., Hanson, C., Thompson, D., Yugawa, T., Ruscetti, S. (2005). Activation of the Jun N-Terminal Kinase Pathway by Friend Spleen Focus-Forming Virus and Its Role in the Growth and Survival of Friend Virus-Induced Erythroleukemia Cells. J. Virol. 79: 12752-12762 [Abstract] [Full Text]  
  • Shaked, Y., Cervi, D., Neuman, M., Chen, L., Klement, G., Michaud, C. R., Haeri, M., Pak, B. J., Kerbel, R. S., Ben-David, Y. (2005). The splenic microenvironment is a source of proangiogenesis/inflammatory mediators accelerating the expansion of murine erythroleukemic cells. Blood 105: 4500-4507 [Abstract] [Full Text]  
  • Jackers, P., Szalai, G., Moussa, O., Watson, D. K. (2004). Ets-dependent Regulation of Target Gene Expression during Megakaryopoiesis. J. Biol. Chem. 279: 52183-52190 [Abstract] [Full Text]  
  • Ebos, J. M.L., Bocci, G., Man, S., Thorpe, P. E., Hicklin, D. J., Zhou, D., Jia, X., Kerbel, R. S. (2004). A Naturally Occurring Soluble Form of Vascular Endothelial Growth Factor Receptor 2 Detected in Mouse and Human Plasma. Mol Cancer Res 2: 315-326 [Abstract] [Full Text]  
  • Ano, S., Pereira, R., Pironin, M., Lesault, I., Milley, C., Lebigot, I., Quang, C. T., Ghysdael, J. (2004). Erythroblast Transformation by FLI-1 Depends upon Its Specific DNA Binding and Transcriptional Activation Properties. J. Biol. Chem. 279: 2993-3002 [Abstract] [Full Text]  
  • Lebigot, I., Gardellin, P., Lefebvre, L., Beug, H., Ghysdael, J., Quang, C. T. (2003). Up-regulation of SLAP in FLI-1-transformed erythroblasts interferes with EpoR signaling. Blood 102: 4555-4562 [Abstract] [Full Text]  
  • Starck, J., Cohet, N., Gonnet, C., Sarrazin, S., Doubeikovskaia, Z., Doubeikovski, A., Verger, A., Duterque-Coquillaud, M., Morle, F. (2003). Functional Cross-Antagonism between Transcription Factors FLI-1 and EKLF. Mol. Cell. Biol. 23: 1390-1402 [Abstract] [Full Text]  
  • Lelievre, E., Lionneton, F., Mattot, V., Spruyt, N., Soncin, F. (2002). Ets-1 Regulates fli-1 Expression in Endothelial Cells. IDENTIFICATION OF ETS BINDING SITES IN THE fli-1 GENE PROMOTER. J. Biol. Chem. 277: 25143-25151 [Abstract] [Full Text]  
  • Li, Y.-J., Higgins, R. R., Pak, B. J., Shivdasani, R. A., Ney, P. A., Archer, M., Ben-David, Y. (2001). p45NFE2 Is a Negative Regulator of Erythroid Proliferation Which Contributes to the Progression of Friend Virus-Induced Erythroleukemias. Mol. Cell. Biol. 21: 73-80 [Abstract] [Full Text]  
  • Sarrazin, S., Starck, J., Gonnet, C., Doubeikovski, A., Melet, F., Morle, F. (2000). Negative and Translation Termination-Dependent Positive Control of FLI-1 Protein Synthesis by Conserved Overlapping 5' Upstream Open Reading Frames in Fli-1 mRNA. Mol. Cell. Biol. 20: 2959-2969 [Abstract] [Full Text]  
  • Tamir, A., Petrocelli, T., Stetler, K., Chu, W., Howard, J., St. Croix, B., Slingerland, J., Ben-David, Y. (2000). Stem Cell Factor Inhibits Erythroid Differentiation by Modulating the Activity of G1-Cyclin-dependent Kinase Complexes: A Role for p27 in Erythroid Differentiation Coupled G1 Arrest. Cell Growth Differ. 11: 269-277 [Abstract] [Full Text]  
  • Nozawa, M., Yomogida, K., Kanno, N., Nonomura, N., Miki, T., Okuyama, A., Nishimune, Y., Nozaki, M. (2000). Prostate-specific Transcription Factor hPSE Is Translated Only in Normal Prostate Epithelial Cells. Cancer Res. 60: 1348-1352 [Abstract] [Full Text]  
  • Jiang, Z., Guo, Z., Saad, F. A., Ellis, J., Zacksenhaus, E. (2001). Retinoblastoma Gene Promoter Directs Transgene Expression Exclusively to the Nervous System. J. Biol. Chem. 276: 593-600 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»