The transcription factor PU.1 is involved in macrophage proliferation

Antonio Celada, Francesc E. Borràs, Concepció Soler, Jorge Lloberas, Michael Klemsz, Charles Van Beveren, Scott McKercher, Richard A. Maki

Research output: Contribution to journalArticle

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Abstract

PU.1 is a tissue-specific transcription factor that is expressed in cells of the hematopoietic lineage including macrophages, granulocytes, and B lymphocytes. Bone marrow-derived macrophages transfected with an antisense PU.1 expression construct or treated with antisense oligonucleotides showed a decrease in proliferation compared with controls. In contrast, bone marrow macrophages transfected with a sense PU.1 expression construct displayed enhanced macrophage colony-stimulating factor (M-CSF)-dependent proliferation. Interestingly, there was no effect of sense or antisense constructs of PU.1 on the proliferation of the M-CSF-independent cell line, suggesting that the response was M-CSF dependent. This was further supported by the finding that macrophages transfected with a sense or an antisense PU.1 construct showed, respectively, an increased or a reduced level of surface expression of receptors for M-CSF. The enhancement of proliferation seems to be selective for PU.1, since transfections with several other members of the ets family, including ets-2 and tli-1, had no effect. Various mutants of PU.1 were also tested for their ability to affect macrophage proliferation. A reduction in macrophage proliferation was found when cells were transfected with a construct in which the DNA-binding domain of PU.1 was expressed. The PEST (proline-, glutamic acid-, serine-, and threonine-rich region) sequence of the PU.1 protein, which is an important domain for protein-protein interactions in B cells, was found to have no influence on PU.1-enhanced macrophage proliferation when an expression construct containing PU.1 minus the PEST domain was transfected into bone marrow-derived macrophages. In vivo, PU.1 is phosphorylated on several serine residues. The transfection of plasmids containing PU.1 with mutations at each of five serines showed that only positions 41 and 45 are critical for enhanced macrophage proliferation. We conclude that PU.1 is necessary for the M-CSF-dependent proliferation of macrophages. One of the proliferation-relevant targets of this transcription factor could be the M-CSF receptor.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalJournal of Experimental Medicine
Volume184
Issue number1
DOIs
StatePublished - Jul 1 1996

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Macrophages
Macrophage Colony-Stimulating Factor
Macrophage Colony-Stimulating Factor Receptors
Serine
Transfection
B-Lymphocytes
Transcription Factors
proto-oncogene protein Spi-1
Protein Interaction Domains and Motifs
Aptitude
Antisense Oligonucleotides
Cell Lineage
Threonine
Granulocytes
Proline
Glutamic Acid
Plasmids
Bone Marrow
Cell Line
Mutation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Celada, A., Borràs, F. E., Soler, C., Lloberas, J., Klemsz, M., Van Beveren, C., ... Maki, R. A. (1996). The transcription factor PU.1 is involved in macrophage proliferation. Journal of Experimental Medicine, 184(1), 61-69. https://doi.org/10.1084/jem.184.1.61

The transcription factor PU.1 is involved in macrophage proliferation. / Celada, Antonio; Borràs, Francesc E.; Soler, Concepció; Lloberas, Jorge; Klemsz, Michael; Van Beveren, Charles; McKercher, Scott; Maki, Richard A.

In: Journal of Experimental Medicine, Vol. 184, No. 1, 01.07.1996, p. 61-69.

Research output: Contribution to journalArticle

Celada, A, Borràs, FE, Soler, C, Lloberas, J, Klemsz, M, Van Beveren, C, McKercher, S & Maki, RA 1996, 'The transcription factor PU.1 is involved in macrophage proliferation', Journal of Experimental Medicine, vol. 184, no. 1, pp. 61-69. https://doi.org/10.1084/jem.184.1.61
Celada, Antonio ; Borràs, Francesc E. ; Soler, Concepció ; Lloberas, Jorge ; Klemsz, Michael ; Van Beveren, Charles ; McKercher, Scott ; Maki, Richard A. / The transcription factor PU.1 is involved in macrophage proliferation. In: Journal of Experimental Medicine. 1996 ; Vol. 184, No. 1. pp. 61-69.
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