Activating transcription factor 2 is necessary for maximal activity and serum induction of the cyclin A promoter in chondrocytes.
Endochondral bone growth is regulated through the proliferation and differentiation of growth plate chondrocytes. Mice deficient for the activating transcription factor 2 (ATF-2) gene show reduced proliferation of chondrocytes. Here we demonstrate that the cyclin A gene is a target of ATF-2 in chondrocytes. Serum stimulation of chondrogenic rat chondrosarcoma cells induces cyclin A expression. A cyclic AMP response element (CRE) is necessary for optimal activity and serum inducibility of the cyclin A promoter and confers regulation by ATF-2. Phosphorylation and activity of ATF-2 are enhanced dramatically upon serum stimulation of rat chondrosarcoma cells. Mutation of the CRE or overexpression of dominant-negative ATF-2 inhibits serum induction of the cyclin A promoter. Chondrocytes from ATF-2-deficient mice display reduced and delayed induction of cyclin A upon serum stimulation. The ATF-2-related transcription factor CRE- binding protein contributes to the activity of the cyclin A CRE in chondrocytes, whereas c-Jun and c-Fos regulate the promoter independently of the CRE. Our data suggest that the reduction in cyclin A levels in chondrocytes from ATF-2-deficient mice contributes to their phenotype of reduced chondrocyte proliferation and dwarfism.[1]References
- Activating transcription factor 2 is necessary for maximal activity and serum induction of the cyclin A promoter in chondrocytes. Beier, F., Taylor, A.C., LuValle, P. J. Biol. Chem. (2000) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
