Molecular and Genetic Interactions between CCN2 and CCN3 behind Their Yin-Yang Collaboration

• Published in: International journal of molecular sciences Vol. 23; no. 11; p. 5887
• Main Authors: Kubota, Satoshi, Kawata, Kazumi, Hattori, Takako, Nishida, Takashi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.05.2022; MDPI
• Subjects: Biomolecules; Cartilage; CCN2; CCN3; Cell adhesion & migration; Cell growth; Cell Proliferation; cellular communication network factor; Cofactors; Collaboration; Communications networks; Connective tissue growth factor; Connective Tissue Growth Factor - genetics; Connective Tissue Growth Factor - metabolism; Energy metabolism; Extracellular matrix; Fibroblasts; Fibrosis; Gene expression; Gene Expression Regulation; Gene regulation; Glycolysis; Heparan sulfate; Humans; Insulin-like growth factors; Kinases; Ligands; Microenvironments; Molecular interactions; Names; Nephroblastoma Overexpressed Protein - genetics; Nephroblastoma Overexpressed Protein - metabolism; Organs; Proteins; Review; Yin-Yang; cellular communication network factor; CCN3; fibrosis; CCN2; cartilage; glycolysis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23115887

Cellular communication network factor (CCN) 2 and 3 are the members of the CCN family that conduct the harmonized development of a variety of tissues and organs under interaction with multiple biomolecules in the microenvironment. Despite their striking structural similarities, these two members show contrastive molecular functions as well as temporospatial emergence in living tissues. Typically, CCN2 promotes cell growth, whereas CCN3 restrains it. Where CCN2 is produced, CCN3 disappears. Nevertheless, these two proteins collaborate together to execute their mission in a yin-yang fashion. The apparent functional counteractions of CCN2 and CCN3 can be ascribed to their direct molecular interaction and interference over the cofactors that are shared by the two. Recent studies have revealed the mutual negative regulation systems between CCN2 and CCN3. Moreover, the simultaneous and bidirectional regulatory system of CCN2 and CCN3 is also being clarified. It is of particular note that these regulations were found to be closely associated with glycolysis, a fundamental procedure of energy metabolism. Here, the molecular interplay and metabolic gene regulation that enable the yin-yang collaboration of CCN2 and CCN3 typically found in cartilage development/regeneration and fibrosis are described.