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

Authors

  • Qin Ma,

    1. Department of Anatomy and Cell Biology, College of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, Florida 32610-0235
    Current affiliation:
    1. Department of Oral and Maxillofacial Surgery, Dental Hospital, The Fourth Military Medical University, Xi'an, China, 710032.
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  • Xinying Li,

    1. Department of Anatomy and Cell Biology, College of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, Florida 32610-0235
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  • Dustin Vale-Cruz,

    1. Department of Anatomy and Cell Biology, College of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, Florida 32610-0235
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  • Mark L. Brown,

    1. Department of Anatomy and Cell Biology, College of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, Florida 32610-0235
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  • Frank Beier,

    1. CIHR Group in Skeletal Development and Remodeling, Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada N6A 5C1
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  • Phyllis LuValle

    Corresponding author
    1. Department of Anatomy and Cell Biology, College of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, Florida 32610-0235
    • Department of Anatomy and Cell Biology, PO Box 100235, 1600 SW Archer Rd, Gainesville, FL 32610-0235.
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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. © 2007 Wiley-Liss, Inc.

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