The transcription factor PU.1 is involved in macrophage proliferation

doi:10.1084/jem.184.1.61

This Article

	Full Text (PDF, 902K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Celada, A.
	Articles by Maki, R. A.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Celada, A.
	Articles by Maki, R. A.


Social Bookmarking

	What's this?

ARTICLES

The transcription factor PU.1 is involved in macrophage proliferation

A Celada, FE Borras, C Soler, J Lloberas, M Klemsz, C van Beveren, S McKercher and RA Maki
Departament de Fisiologia (Immunologia), Facultat de Biologia, Universitat de Barcelona, Spain.

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 fli-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.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Tsubakimoto, Y., Yamada, H., Yokoi, H., Kishida, S., Takata, H., Kawahito, H., Matsui, A., Urao, N., Nozawa, Y., Hirai, H., Imanishi, J., Ashihara, E., Maekawa, T., Takahashi, T., Okigaki, M., Matsubara, H. (2009). Bone Marrow Angiotensin AT1 Receptor Regulates Differentiation of Monocyte Lineage Progenitors From Hematopoietic Stem Cells. Arterioscler. Thromb. Vasc. Bio. 29: 1529-1536 [Abstract] [Full Text]
Sebastian, C., Herrero, C., Serra, M., Lloberas, J., Blasco, M. A., Celada, A. (2009). Telomere Shortening and Oxidative Stress in Aged Macrophages Results in Impaired STAT5a Phosphorylation. J. Immunol. 183: 2356-2364 [Abstract] [Full Text]
Espia, M., Sebastian, C., Mulero, M., Giralt, M., Mallol, J., Celada, A., Lloberas, J. (2008). Granulocyte Macrophage-Colony-Stimulating Factor-Dependent Proliferation Is Impaired in Macrophages From Senescence-Accelerated Mice. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 63: 1161-1167 [Abstract] [Full Text]
Valledor, A. F., Arpa, L., Sanchez-Tillo, E., Comalada, M., Casals, C., Xaus, J., Caelles, C., Lloberas, J., Celada, A. (2008). IFN-{gamma}-mediated inhibition of MAPK phosphatase expression results in prolonged MAPK activity in response to M-CSF and inhibition of proliferation. Blood 112: 3274-3282 [Abstract] [Full Text]
Sebastian, C., Serra, M., Yeramian, A., Serrat, N., Lloberas, J., Celada, A. (2008). Deacetylase Activity Is Required for STAT5-Dependent GM-CSF Functional Activity in Macrophages and Differentiation to Dendritic Cells. J. Immunol. 180: 5898-5906 [Abstract] [Full Text]
Valledor, A. F., Sanchez-Tillo, E., Arpa, L., Park, J. M., Caelles, C., Lloberas, J., Celada, A. (2008). Selective Roles of MAPKs during the Macrophage Response to IFN-{gamma}. J. Immunol. 180: 4523-4529 [Abstract] [Full Text]
Casals, C., Barrachina, M., Serra, M., Lloberas, J., Celada, A. (2007). Lipopolysaccharide Up-Regulates MHC Class II Expression on Dendritic Cells through an AP-1 Enhancer without Affecting the Levels of CIITA. J. Immunol. 178: 6307-6315 [Abstract] [Full Text]
Sanchez-Tillo, E., Comalada, M., Xaus, J., Farrera, C., Valledor, A. F., Caelles, C., Lloberas, J., Celada, A. (2007). JNK1 Is Required for the Induction of Mkp1 Expression in Macrophages during Proliferation and Lipopolysaccharide-dependent Activation. J. Biol. Chem. 282: 12566-12573 [Abstract] [Full Text]
Liu, J., Ma, X. (2006). Interferon Regulatory Factor 8 Regulates RANTES Gene Transcription in Cooperation with Interferon Regulatory Factor-1, NF-{kappa}B, and PU.1. J. Biol. Chem. 281: 19188-19195 [Abstract] [Full Text]
Sanchez-Tillo, E., Comalada, M., Farrera, C., Valledor, A. F., Lloberas, J., Celada, A. (2006). Macrophage-Colony-Stimulating Factor-Induced Proliferation and Lipopolysaccharide-Dependent Activation of Macrophages Requires Raf-1 Phosphorylation to Induce Mitogen Kinase Phosphatase-1 Expression.. J. Immunol. 176: 6594-6602 [Abstract] [Full Text]
Himes, S. R., Sester, D. P., Ravasi, T., Cronau, S. L., Sasmono, T., Hume, D. A. (2006). The JNK Are Important for Development and Survival of Macrophages. J. Immunol. 176: 2219-2228 [Abstract] [Full Text]
Bai, Y., Srinivasan, L., Perkins, L., Atchison, M. L. (2005). Protein Acetylation Regulates Both PU.1 Transactivation and Ig{kappa} 3' Enhancer Activity. J. Immunol. 175: 5160-5169 [Abstract] [Full Text]
Le Scolan, E., Pchejetski, D., Banno, Y., Denis, N., Mayeux, P., Vainchenker, W., Levade, T., Moreau-Gachelin, F. (2005). Overexpression of sphingosine kinase 1 is an oncogenic event in erythroleukemic progression. Blood 106: 1808-1816 [Abstract] [Full Text]
Luo, Q., Ma, X., Wahl, S. M., Bieker, J. J., Crossley, M., Montaner, L. J. (2004). Activation and Repression of Interleukin-12 p40 Transcription by Erythroid Kruppel-like Factor in Macrophages. J. Biol. Chem. 279: 18451-18456 [Abstract] [Full Text]
Trapnell, B. C., Whitsett, J. A., Nakata, K. (2003). Pulmonary Alveolar Proteinosis. NEJM 349: 2527-2539 [Full Text]
Comalada, M., Xaus, J., Valledor, A. F., Lopez-Lopez, C., Pennington, D. J., Celada, A. (2003). PKC{epsilon} is involved in JNK activation that mediates LPS-induced TNF-{alpha}, which induces apoptosis in macrophages. Am. J. Physiol. Cell Physiol. 285: C1235-C1245 [Abstract] [Full Text]
Comalada, M., Cardo, M., Xaus, J., Valledor, A. F., Lloberas, J., Ventura, F., Celada, A. (2003). Decorin Reverses the Repressive Effect of Autocrine-Produced TGF-{beta} on Mouse Macrophage Activation. J. Immunol. 170: 4450-4456 [Abstract] [Full Text]
Wang, J.-M., Lai, M.-Z., Yang-Yen, H.-F. (2003). Interleukin-3 Stimulation of mcl-1 Gene Transcription Involves Activation of the PU.1 Transcription Factor through a p38 Mitogen-Activated Protein Kinase-Dependent Pathway. Mol. Cell. Biol. 23: 1896-1909 [Abstract] [Full Text]
Du, J., Stankiewicz, M. J., Liu, Y., Xi, Q., Schmitz, J. E., Lekstrom-Himes, J. A., Ackerman, S. J. (2002). Novel Combinatorial Interactions of GATA-1, PU.1, and C/EBPepsilon Isoforms Regulate Transcription of the Gene Encoding Eosinophil Granule Major Basic Protein. J. Biol. Chem. 277: 43481-43494 [Abstract] [Full Text]
Kallies, A., Rosenbauer, F., Scheller, M., Knobeloch, K.-P., Horak, I. (2002). Accumulation of c-Cbl and rapid termination of colony-stimulating factor 1 receptor signaling in interferon consensus sequence binding protein-deficient bone marrow-derived macrophages. Blood 99: 3213-3219 [Abstract] [Full Text]
Xaus, J., Comalada, M., Cardo, M., Valledor, A. F., Celada, A. (2001). Decorin inhibits macrophage colony-stimulating factor proliferation of macrophages and enhances cell survival through induction of p27Kip1 and p21Waf1. Blood 98: 2124-2133 [Abstract] [Full Text]
Grazia Cappiello, M., Sutterwala, F. S., Trinchieri, G., Mosser, D. M., Ma, X. (2001). Suppression of IL-12 Transcription in Macrophages Following Fc{{gamma}} Receptor Ligation. J. Immunol. 166: 4498-4506 [Abstract] [Full Text]
Maitra, S., Atchison, M. (2000). BSAP Can Repress Enhancer Activity by Targeting PU.1 Function. Mol. Cell. Biol. 20: 1911-1922 [Abstract] [Full Text]
Valledor, A. F., Comalada, M., Xaus, J., Celada, A. (2000). The Differential Time-course of Extracellular-regulated Kinase Activity Correlates with the Macrophage Response toward Proliferation or Activation. J. Biol. Chem. 275: 7403-7409 [Abstract] [Full Text]
Xaus, J., Valledor, A. F., Cardo, M., Marques, L., Beleta, J., Palacios, J. M., Celada, A. (1999). Adenosine Inhibits Macrophage Colony-Stimulating Factor-Dependent Proliferation of Macrophages Through the Induction of p27kip-1 Expression. J. Immunol. 163: 4140-4149 [Abstract] [Full Text]
Valledor, A. F., Xaus, J., Marques, L., Celada, A. (1999). Macrophage Colony-Stimulating Factor Induces the Expression of Mitogen-Activated Protein Kinase Phosphatase-1 Through a Protein Kinase C-Dependent Pathway. J. Immunol. 163: 2452-2462 [Abstract] [Full Text]
Henkel, G. W., McKercher, S. R., Leenen, P. J.M., Maki, R. A. (1999). Commitment to the Monocytic Lineage Occurs in the Absence of the Transcription Factor PU.1. Blood 93: 2849-2858 [Abstract] [Full Text]
Rao, S., Matsumura, A., Yoon, J., Simon, M. C. (1999). SPI-B Activates Transcription via a Unique Proline, Serine, and Threonine Domain and Exhibits DNA Binding Affinity Differences from PU.1. J. Biol. Chem. 274: 11115-11124 [Abstract] [Full Text]
Behre, G., Whitmarsh, A. J., Coghlan, M. P., Hoang, T., Carpenter, C. L., Zhang, D.-E., Davis, R. J., Tenen, D. G. (1999). c-Jun Is a JNK-independent Coactivator of the PU.1 Transcription Factor. J. Biol. Chem. 274: 4939-4946 [Abstract] [Full Text]
Fisher, R. C., Olson, M. C., Pongubala, J. M.�R., Perkel, J. M., Atchison, M. L., Scott, E. W., Simon, M. C. (1998). Normal Myeloid Development Requires Both the Glutamine-Rich Transactivation Domain and the PEST Region of Transcription Factor PU.1 but Not the Potent Acidic Transactivation Domain. Mol. Cell. Biol. 18: 4347-4357 [Abstract] [Full Text]
Tenen, D. G., Hromas, R., Licht, J. D., Zhang, D.-E. (1997). Transcription Factors, Normal Myeloid Development, and Leukemia. Blood 90: 489-519 [Full Text]
Rieske, P., Pongubala, J. M. R. (2001). AKT Induces Transcriptional Activity of PU.1 through Phosphorylation-mediated Modifications within Its Transactivation Domain. J. Biol. Chem. 276: 8460-8468 [Abstract] [Full Text]