The 1,25(OH)2D3-Regulated Transcription Factor MN1 Stimulates Vitamin D Receptor-Mediated Transcription and Inhibits Osteoblastic Cell Proliferation

Amelia L. M. Sutton, Xiaoxue Zhang, Tara I. Ellison, Paul N. MacDonald
2005 Molecular Endocrinology  
The vitamin D endocrine system is essential for maintaining mineral ion homeostasis and preserving bone density. The most bioactive form of vitamin D, 1,25-dihydroxyvitamin D 3 [1,25-(OH) 2 D 3 ] elicits its effects by binding to the vitamin D receptor (VDR) and regulating the transcription of target genes. In osteoblasts, the bone-forming cells of the skeleton, 1,25-(OH) 2 D 3 regulates cell proliferation, differentiation, and mineralization of the extracellular matrix. Despite these
more » ... cterized biological functions, relatively few 1,25-(OH) 2 D 3 target genes have been described in osteoblasts. In this study, we characterize the regulation and function of MN1, a novel 1,25-(OH) 2 D 3induced gene in osteoblastic cells. MN1 is a nuclear protein first identified as a gene disrupted in First Published Online May 12, 2005 Abbreviations: BrdU, 5-Bromo-2Ј-deoxyuridine; CBP, cAMP response element binding protein (CREB)-binding protein; DBD, DNA binding domain; DRIP, VDR-interacting protein; EGFP, enhanced green fluorescent protein; GR, glucocorticoid receptor; GRIP, GR-interacting protein; LBD, ligand-binding domain; MN1, gene disrupted in meningioma-1; MSV-LTR, Moloney sarcoma virus long terminal repeat; NCoA-62, nuclear coactivator 62 kDa; 1,25(OH) 2 D 3 , 1,25-dihydroxyvitamin D 3 ; RAR, retinoic acid receptor; RARE, retinoic acid response element; ROR␤, RAR-related orphan receptor; RXR, retinoid X receptor; SKIP, ski-interacting protein; SRC-1, steroid receptor coactivator-1; VDR, vitamin D receptor; VDRE, vitamin D response element. Molecular Endocrinology is published monthly by The Endocrine Society (, the foremost professional society serving the endocrine community.
doi:10.1210/me.2005-0081 pmid:15890672 fatcat:23poj4i35rfatgsjtebxiqyjq4