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Activating transcription factor 2 controls Bcl‐2 promoter activity in growth plate chondrocytes
Author(s) -
Ma Qin,
Li Xinying,
ValeCruz Dustin,
Brown Mark L.,
Beier Frank,
LuValle Phyllis
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21198
Subject(s) - transcription factor , promoter , chondrocyte , microbiology and biotechnology , activating transcription factor , activating transcription factor 2 , cyclin d1 , biology , creb , response element , ap 1 transcription factor , apoptosis , gene , gene expression , cell cycle , genetics , in vitro
Activating transcription factor 2 (ATF‐2) is expressed ubiquitously in mammals. Mice deficient in ATF‐2 (ATF‐2 m/m) are slightly smaller than their normal littermates at birth. Approximately 50% of mice born mutant in both alleles die within the first month. Those that survive develop a hypochondroplasia‐like dwarfism, characterized by shortened growth plates and kyphosis. Expression of ATF‐2 within the growth plate is limited to the resting and proliferating zones. We have previously shown that ATF‐2 targets the cyclic AMP response element (CRE) in the promoters of cyclin A and cyclin D1 in growth plate chondrocytes to activate their expression. Here, we demonstrate that Bcl‐2, a cell death inhibitor that regulates apoptosis, is expressed within the growth plate in proliferative and prehypertrophic chondrocytes. However, Bcl‐2 expression declines in hypertrophic chondrocytes. The Bcl‐2 promoter contains a CRE at −1,552 bp upstream of the translation start. Mutations within this CRE cause reduced Bcl‐2 promoter activity. We show here that the absence of ATF‐2 in growth plate chondrocytes corresponds to a decline in Bcl‐2 promoter activity, as well as a reduction in Bcl‐2 protein levels. In addition, we show that ATF‐2 as well as CREB, a transcription factor that can heterodimerize with ATF‐2, bind to the CRE within the Bcl‐2 promoter. These data identify the Bcl‐2 gene as a novel target of ATF‐2 and CREB in growth plate chondrocytes. J. Cell. Biochem. 101: 477–487, 2007. © 2007 Wiley‐Liss, Inc.