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

20 Citations (Scopus)

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

Fingerprint

Cell Survival
Macrophages
Cells
Cell Proliferation
Activity Cycles
Gene Knockout Techniques
Cell Cycle Checkpoints
S Phase
Workplace
Cell Cycle
Genes
Bone Marrow
Cell proliferation
Bone

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Trikha, P., Sharma, N., Opavsky, R., Reyes, A., Pena, C., Ostrowski, M. C., ... 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

E2f1-3 are critical for myeloid development. / Trikha, Prashant; Sharma, Nidhi; Opavsky, Rene; Reyes, Andres; Pena, Clarissa; Ostrowski, Michael C.; Roussel, Martine F.; Leone, Gustavo.

In: Journal of Biological Chemistry, Vol. 286, No. 6, 11.02.2011, p. 4783-4795.

Research output: Contribution to journalArticle

Trikha, P, Sharma, N, Opavsky, R, Reyes, A, Pena, C, Ostrowski, MC, Roussel, MF & Leone, G 2011, 'E2f1-3 are critical for myeloid development', Journal of Biological Chemistry, vol. 286, no. 6, pp. 4783-4795. https://doi.org/10.1074/jbc.M110.182733
Trikha P, Sharma N, Opavsky R, Reyes A, Pena C, Ostrowski MC et al. E2f1-3 are critical for myeloid development. Journal of Biological Chemistry. 2011 Feb 11;286(6):4783-4795. https://doi.org/10.1074/jbc.M110.182733
Trikha, Prashant ; Sharma, Nidhi ; Opavsky, Rene ; Reyes, Andres ; Pena, Clarissa ; Ostrowski, Michael C. ; Roussel, Martine F. ; Leone, Gustavo. / E2f1-3 are critical for myeloid development. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 6. pp. 4783-4795.
@article{8d7bd978be804050a75e6fd355a45522,
title = "E2f1-3 are critical for myeloid development",
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.",
author = "Prashant Trikha and Nidhi Sharma and Rene Opavsky and Andres Reyes and Clarissa Pena and Ostrowski, {Michael C.} and Roussel, {Martine F.} and Gustavo Leone",
year = "2011",
month = "2",
day = "11",
doi = "10.1074/jbc.M110.182733",
language = "English (US)",
volume = "286",
pages = "4783--4795",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "6",

}

TY - JOUR

T1 - E2f1-3 are critical for myeloid development

AU - Trikha, Prashant

AU - Sharma, Nidhi

AU - Opavsky, Rene

AU - Reyes, Andres

AU - Pena, Clarissa

AU - Ostrowski, Michael C.

AU - Roussel, Martine F.

AU - Leone, Gustavo

PY - 2011/2/11

Y1 - 2011/2/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79953010469&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953010469&partnerID=8YFLogxK

U2 - 10.1074/jbc.M110.182733

DO - 10.1074/jbc.M110.182733

M3 - Article

VL - 286

SP - 4783

EP - 4795

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 6

ER -