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Molecular and Cellular Biology, April 1999, p. 2624-2634, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Ets2 Transcription Factor Inhibits Apoptosis Induced by Colony-Stimulating Factor 1 Deprivation of Macrophages through a Bcl-xL-Dependent Mechanism

Lidia Sevilla,1 Christel Aperlo,1,dagger Vjekoslav Dulic,2 Jean Claude Chambard,1 Christel Boutonnet,1,Dagger Olivier Pasquier,1 Philippe Pognonec,1 and Kim E. Boulukos1,*

Centre de Biochimie, Université de Nice, Faculté des Sciences, 06108 Nice,1 and CRBM-CNRS, BP 5051, 34033, Montpellier,2 France

Received 28 May 1998/Returned for modification 15 July 1998/Accepted 20 January 1999

Bcl-xL, a member of the Bcl-2 family, inhibits apoptosis, and its expression is regulated at the transcriptional level, yet nothing is known about the transcription factors specifically activating this promoter. The bcl-x promoter contains potential Ets binding sites, and we show that the transcription factor, Ets2, first identified by its sequence identity to v-ets of the E26 retrovirus, can transactivate the bcl-x promoter. Transient expression of Ets2 results in the upregulation of Bcl-xL but not of Bcl-xS, an alternatively spliced gene product which induces apoptosis. Ets2 is ubiquitously expressed at low levels in a variety of cell types and tissues but is specifically induced to abundant levels during macrophage differentiation. Since Bcl-xL is also upregulated during macrophage differentiation, we asked whether the bcl-x could be a direct downstream target gene of Ets2 in macrophages. BAC1.2F5 macrophages, which are dependent on macrophage colony-stimulating factor 1 (CSF-1) for their growth and survival, were used in these studies. We show that CSF-1 stimulation of BAC1.2F5 macrophages results in the upregulation of expression of ets2 and bcl-xL with similar kinetics of induction. In the absence of CSF-1, these macrophages undergo cell death by apoptosis, whereas constitutive expression of Ets2 rescues these cells from cell death, and bcl-xL is upregulated. These results strongly suggest a novel role of Ets2 in affecting apoptosis through its regulation of Bcl-xL transcription.

* Corresponding author. Mailing address: Centre de Biochimie, Faculté des Sciences, 06108 Nice, France. Phone and fax: 33 4 92 07 64 13. E-mail: boulukos{at}unice.fr.

dagger Present address: Dana Farber Cancer Institute, Department of Adult Oncology, Boston, MA 02115.

Dagger Present address: Swiss Institute for Experimental Cancer Research, CH-1066 Epalinges, Switzerland.

Molecular and Cellular Biology, April 1999, p. 2624-2634, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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