Affiliation:
1. Centre de Biochimie, Université de Nice, Faculté des Sciences, 06108 Nice, 1 and
2. CRBM-CNRS, BP 5051, 34033, Montpellier, 2 France
Abstract
ABSTRACT
Bcl-x
L
, 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-x
L
but not of Bcl-x
S
, 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-x
L
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-x
L
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-x
L
is upregulated. These results strongly suggest a novel role of Ets2 in affecting apoptosis through its regulation of Bcl-x
L
transcription.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
74 articles.
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