E2f1-3 are critical for myeloid development

Prashant Trikha, Nidhi Sharma, Rene Opavsky, Andres Reyes, Clarissa Pena, Michael C. Ostrowski, Martine F. Roussel, Gustavo Leone

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Hematopoietic development involves the coordinated activity of differentiation and cell cycle regulators. In current models of mammalian cell cycle control, E2f activators (E2f1, E2f2, and E2f3) are portrayed as the ultimate transcriptional effectors that commit cells to enter and progress through S phase. Using conditional gene knock-out strategies, we show that E2f1-3 are not required for the proliferation of early myeloid progenitors. Rather, these E2fs are critical for cell survival and proliferation at two distinct steps of myeloid development. First, E2f1-3 are required as transcriptional repressors for the survival of CD11b+ myeloid progenitors, and then they are required as activators for the proliferation of CD11b+ macrophages. In bone marrow macrophages, we show that E2f1-3 respond to CSF1-Myc mitogenic signals and serve to activate E2f target genes and promote their proliferation. Together, these findings expose dual functions for E2f1-3 at distinct stages of myeloid development in vivo, first as repressors in cell survival and then as activators in cell proliferation. In summary, this work places E2f1-3 in a specific signaling cascade that is critical for myeloid development in vivo.

Original languageEnglish (US)
Pages (from-to)4783-4795
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number6
DOIs
StatePublished - Feb 11 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Trikha, P., Sharma, N., Opavsky, R., Reyes, A., Pena, C., Ostrowski, M. C., Roussel, M. F., & Leone, G. (2011). E2f1-3 are critical for myeloid development. Journal of Biological Chemistry, 286(6), 4783-4795. https://doi.org/10.1074/jbc.M110.182733