Osteoblast differentiation This protein is a member of the<unk> family of transcription factors and has a Runt DNA-binding domain. It is essential for osteoblastic differentiation and skeletal morphogenesis. It acts 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. Transcript variants of the gene that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing. The cellular dynamics of<unk>  protein are also important for proper osteoblast differentiation.<unk>  protein is detected in preosteoblasts and the expression is upregulated in immature osteoblasts and downregulated in mature osteoblasts. It is the first transcription factor required for determination of osteoblast commitment, followed by Sp7 and Wnt-signaling.<unk>  is responsible for inducing the differentiation of multipotent mesenchymal cells into immature osteoblasts, as well as activating expression of several key downstream proteins that maintain osteoblast differentiation and bone matrix genes. Knock-out of the DNA-binding activity results in inhibition of osteoblastic differentiation. Because of this,<unk>  is often referred to as the master regulator of bone. Cell cycle regulation In addition to being the master regulator of osteoblast differentiation,<unk>  has also been shown to play several roles in cell cycle regulation. This is due, in part, to the fact that<unk>  interacts with many cellular proliferation genes on a transcription level, such as c-Myb and C/EBP, as well as p53/ These functions are critical for osteoblast proliferation and maintenance. This is often controlled via oscillating levels of<unk>  within throughout cell cycle due to regulated degradation and transcriptional activity. Oscillating levels of<unk>  within the cell contribute to cell cycle dynamics. In the MC3T3-E1 osteoblast cell line,<unk>  levels are a maximum during G1 and a minimum during G2, S, and mitosis. In addition, the oscillations in<unk>  contribute to G1-related anti-proliferative function. It has also been proposed that decreasing levels of<unk>  leads to cell cycle exit for proliferating and differentiating osteoblasts, and that<unk>  plays a role in mediating the final stages of osteoblast via this mechanism. Current research posits that the levels of<unk>  serve various functions. In addition,<unk>  has been shown to interact with several kinases that contribute to facilitate cell-cycle dependent dynamics via direct protein phosphorylation. Furthermore,<unk>  controls the gene expression of cyclin D2, D3, and the CDK inhibitor p21(cip1) in hematopoietic cells. It has been shown that on a molecular level,<unk> associates with the cdc2 partner cyclin B1 during mitosis. The phosphorylation state of<unk>  also mediates its DNA-binding activity. The<unk>  DNA-binding activity is correlated with cellular proliferation, which suggests<unk>  phosphorylation may also be related to<unk> -mediated cellular proliferation and cell cycle control. To support this, it has been noted that<unk> is phosphorylated at Ser451 by cdc2 kinase, which facilitates cell cycle progression through the regulation of G2 and M phases. Schematic of<unk>  Levels During Cell Cycle Progression
RUNX2
SOX2
BMPR1A
CDK13
SPATA16
KRAS
WRAP53
Kras