원문정보
초록
영어
CREB/ATF bZip transcription factor (CREBZF, SMILE) is a member of the mammalian ATF/CREB family of transcription factors and an orphan nuclear receptor. Recent studies have suggested that CREBZF is a novel co-repressor that is involved in nuclear receptor signaling; however, the role of CREBZF in osteoblast differentiation has not discovered yet. This study demonstrates that CREBZF suppressed osteoblast differentiation by regulating activity of Runt-related transcription factor-2 (RUNX2). Tunicamycin, a stimulator of ER-stress, induced expression of CREBZF. Bone morphogenetic protein-2 (BMP2) inhibits the expression of CREBZF, and BMP2-induced expression of alkaline phosphatase and osteocalcin, osteogenic marker genes, was suppressed by CREBZF. The molecular mechanism of CREBZF in differentiation of osteoblast was also determined. An immunoprecipitation assay revealed a physical interaction between CREBZF and RUNX2 that significantly impaired RUNX2-dependent activation of the osteocalcin gene. A ChIP assay revealed that CREBZF repressed the ability of RUNX2 to bind to the osteocalcin gene promoter. Taken together, these findings demonstrate that CREBZF negatively regulates osteocalcin via a direct interaction with RUNX2.