Title

Activating transcription factor 2 controls Bcl-2 promoter activity in growth plate chondrocytes

Document Type

Journal Article

Faculty

Faculty of Computing, Health and Science

School

School of Exercise, Biomedical and Health Science

RAS ID

9700

Comments

Ma, Q., Li, X., Vale‐Cruz, D., Brown, M. L., Beier, F., & LuValle, P. (2007). Activating transcription factor 2 controls Bcl‐2 promoter activity in growth plate chondrocytes. Journal of cellular biochemistry, 101(2), 477-487.

Abstract

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.

DOI

10.1002/jcb.21198

 
COinS
 

Link to publisher version (DOI)

10.1002/jcb.21198