NOG

What is NOG protein?

NOG (noggin) gene is a protein coding gene which situated on the long arm of chromosome 17 at locus 17q22. The protein appears to have pleiotropic effect, both early in development as well as in later stages. It was originally isolated from Xenopus based on its ability to restore normal dorsal-ventral body axis in embryos that had been artificially ventralized by UV treatment. The results of the mouse knockout of the ortholog suggest that it is involved in numerous developmental processes, such as neural tube fusion and joint formation. The NOG protein is consisted of 232 amino acids and its molecular mass is approximately 25.8 kDa.

What is the function of NOG protein?

NOG is an antagonist of bone morphogenetic proteins (BMPs), which are part of the transforming growth factor-beta (TGF-β) superfamily. The primary function of NOG protein is to bind and inactivate BMPs, thereby modulating the BMP signaling pathway. In the context of bone and cartilage formation, NOG protein plays a significant role. It can effectively attenuate osteoarthritis (OA) by protecting cartilage and preventing its degradation, as indicated by research that demonstrates the therapeutic potential of NOG protein in treating OA. Furthermore, NOG protein is involved in numerous developmental processes such as neural tube fusion and joint formation. In addition to its role in development and bone metabolism, NOG protein is also used in the field of organoid culture. It is added to the culture medium to coordinate Wnt signal activation in stem cells, promoting their proliferation.

NOG Related Signaling Pathway

NOG can bind and inhibit the binding of Wnt protein to LRP5/6 receptor, thereby preventing Wnt protein from entering the cell and further inhibiting the activation of β-catenin, thereby inhibiting the Wnt/β-catenin signaling pathway. NOG can bind and inhibit the binding of BMP protein to its receptor, thereby preventing BMP protein from entering the cell and further inhibiting the activation of Smad protein. NOG can bind and activate the FGF receptor, thereby further activating the FGF signaling pathway and promoting cell proliferation and differentiation. NOG can bind and activate TGF-β receptors, thereby further activating the TGF-β signaling pathway and promoting cell proliferation and differentiation.

Fig1. BMP signalling. (Bo Kyoung Kang, 2023)

NOG Related Diseases

NOG plays an important role in nervous system development, and its abnormal expression is associated with neural tube defects, hydrocephalus, autism and other neurological developmental disorders. NOG is also involved in the regulation of bone development, and its abnormal expression is associated with spina bifida, polydactyly, osteoporosis and other skeletal abnormalities. The abnormal expression of NOG is associated with the occurrence and development of various tumors, such as breast cancer, gastric cancer, and lung cancer. NOG is also associated with the occurrence and development of some other diseases, such as cardiovascular disease, diabetes, liver disease, etc.

Bioapplications of NOG

Tetrahydropyrimidine (Ectoine) is a cyclic amino acid derived from L-aspartic acid that acts as a protective and stabilizing agent and plays an important role in cells in response to various external pressures, such as high temperature, high osmotic pressure, drying, and radiation. NOG protein has made important progress in the efficient preparation of tetrahydropyrimidine, and through the strategy of combining metabolic engineering and enzyme engineering, it has achieved efficient synthesis in Escherichia coli.

Due to the protective and stabilizing effects of tetrahydropyrimidine, NOG proteins also have applications in the cosmetic industry, especially in the development of products that protect the skin from environmental stress.

Studies have shown that NOG proteins can effectively reduce the condition of osteoarthritis (OA) by protecting the cartilage and preventing its degeneration, which indicates that NOG proteins have potential applications in the treatment of cartilage degenerative diseases such as OA.