Runx2

Introduction

Runx2, also known as Runt-related transcription factor 2, is a protein that in humans is encoded by the RUNX2 gene. It is a key transcription factor associated with osteoblast differentiation and skeletal morphogenesis 1.

Structure

The RUNX2 gene is located on the short (p) arm of chromosome 6 at position 21. RUNX2 protein is composed of 521 amino acids and has a molecular weight of approximately 57 kDa. It contains a Runt DNA-binding domain, which is highly conserved among the RUNX family members. This domain is responsible for the interaction with DNA and other proteins, such as core-binding factor beta (CBFβ) 2.

Function

Runx2 is a master regulator of bone development. It is essential for osteoblast differentiation, chondrocyte maturation, and the expression of many bone matrix genes. Runx2 also plays a role in tooth development and is involved in the regulation of several signaling pathways, including the Wnt and BMP pathways 3.

Role in Disease

Mutations in the RUNX2 gene can lead to a variety of skeletal disorders. The most common is Cleidocranial Dysplasia (CCD), a rare autosomal dominant disorder characterized by delayed closure of cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities 4.

In addition, overexpression of Runx2 has been associated with bone metastasis in several types of cancer, including breast and prostate cancer 5.

Clinical Significance

Due to its crucial role in bone formation and remodeling, Runx2 is a potential therapeutic target for treating bone diseases such as osteoporosis and bone metastasis. Several small molecule inhibitors of Runx2 have been identified and are currently under investigation 6.

References

1. Komori T. Regulation of bone development and extracellular matrix protein genes by RUNX2. Cell Tissue Res. 2010;339(1):189-195. 2. Tahirov TH, Inoue-Bungo T, Morii H, et al. Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta. Cell. 2001;104(5):755-767. 3. Long F. Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol. 2011;13(1):27-38. 4. Otto F, Kanegane H, Mundlos S. Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Hum Mutat. 2002;19(3):209-216. 5. Pratap J, Lian JB, Stein GS. Metastatic bone disease: role of transcription factors and future targets. Bone. 2011;48(1):30-36. 6. Shen R, Wang X, Drissi H, et al. Cyclin D1-cdk4 induce runx2 ubiquitination and degradation. J Biol Chem. 2006;281(24):16347-16353.