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This gene is a member of the RUNX family of transcription factors and encodes a nuclear protein with an Runt DNA-binding domain. This protein is essential for osteoblastic differentiation and skeletal morphogenesis, acting as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Mutations in this gene have been associated with the bone development disorder cleidocranial dysplasia (CCD). Transcript variants, encoding different protein isoforms, result from alternate promoter use as well as alternate splicing. 4 new genes may be under the control of Cbfa1; 3 of them, SelM, elF-4AI, & RPS24, seemed to be linked to a global change in cellular metabolism & cell growth; the CD99/MIC2 gene was strongly overexpressed in cells presenting high levels of Deltacbfa1. Analysis of the three-dimensional structure of the DNA binding runt domain of the RUNX2 protein and its interaction with DNA provide insight into how missense mutations affect RUNX2 function and cause cleidocranial dysplasia. As a target gene of endostatin, cbfa1/osf2 was found to be specifically expressed in granulocytes in human breast neoplasms. Capability of Imatinib to induce an anti-leukemic effect in Core Binding Factor (CBF)-leukemia patients. Cbfa1 is a key regulatory factor in the vascular calcification observed in dialysis patients and is up-regulated in response to many uremic toxins. Cbfa1 is required in mediating the bone anabolic effects of parathyroid hormone. Cleidocranial dysplasia (CCD) is an inherited autosomal-dominant skeletal disease caused by heterozygous mutations in the RUNX2 protein. Cleidocranial dysplasia could result from much smaller losses in the RUNX2 function than has been envisioned on the basis of the conventional haploinsufficiency model. Differential regulation of Cbfa1/Runx2 and osteocalcin gene expression by vitamin-D3, dexamethasone, and local growth factors in primary human osteoblasts. Expression of Runx2 in prostate cancer may be the molecular switch that is associated with expression of various bone-specific factors in prostate cancer. Fidelity of Runx2 intranuclear organization is necessary for expression of target genes that mediate the osteolytic activity of metastatic breast cancer cells. Growth hormone attenuates the transcriptional activity of Runx2 by facilitating its physical association with Stat3beta. Osteocalcin mRNA was down-regulated in Apert osteoblasts carrying the FGFR2 P253R mutation, Runt-related transcription factor-2 (RUNX2) mRNA was differentially spliced, and FGF2 secretion was greater. PLZF plays important roles in early osteoblastic differentiation as an upstream regulator of CBFA1. Physiologic coupling of osteoblast differentiation to cell cycle withdrawal is mediated through runx2 and p27KIP1, and these processes are disrupted in osteosarcoma. RT-PCR analysis of human bone marrow stromal cells during osteogenesis in vitro: the mRNA levels of bone morphogenetic protein-2 (BMP-2), bone sialoprotein-II (BSP), osteopontin (OP) and cbfa-1 increased with culture time in osteogenic medium. RUNX1 and RUNX2 regulate TIMP1 gene expression. RUNX2 DNA binding is regulated by IGF-1 through sequential activation of the PI3K/Pak1 and ERK1/2 signaling cascade. RUNX2 is negatively regulated by the phosphorylation of two conserved serines. Runx2 collaborates with Oct-1 and contributes to the expression of a mammary gland-specific gene. Runx2 expression in breast cancer cells provides a molecular phenotype that enables the interactions between tumor cells and the bone microenvironment that lead to osteolytic disease. Runx2 expression in osteoblasts is reduced by hypoxia, and may be a mechanism of osteoporosis by decreased vascular supply. Runx2 has a role in menin-induced bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation. Runx2 has a role in parathyroid hormone-induced anti-apoptotic signaling in osteoblasts, which is shortened by proteasomal degradation. Runx2 is ectopically expressed in breast cancer cells and that one isoform of Runx2 can activate bsp expression in these cells. Runx2/Cbfa1 activity increases through a posttranslational mechanism involving phosphorylation of key residues and has a role in osteoblastic differentiation. TWIST inactivation reduces expression and DNA binding to the osteocalcin promoter in osteoblasts. Telomerase accelerates osteogenesis of bone marrow stromal stem cells by upregulation of CBFA1, osterix, and osteocalcin. The regulation of SOST expression by Cbfa1 suggests a potential role for the sclerosteosis gene in homeostatic regulation of osteoblast differentiation and function. This protein is regulated by human basic fibroblast growth factor. Clavicular dysplasia was more pronounced with the R19OW mutation, while the bone density was markedly reduced in individuals with either R19OW or deletion of nucleotide C821. Is an essential transcription factor for the regulation of osteoblast differentiation. Mechanical stress plays a key role in the progression of OPLL through an increase in Cbfa1 expression. Regulatory signals are active at transcriptional subnuclear sites. Six novel mutations causing 2 amino acid substitutions and four frameshift mutations were identified in the RUNX2 gene of Italian cleidocranial dysplasia patients. Variants may be related to genetic effects on bone mineral density and osteoporosis.
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