THE COP9 SIGNALOSOME, A NOVEL, ESSENTIAL REGULATOR OF SKELETAL DEVELOPMENT AND TUMORIGENESIS.

In recent years, the evolutionarily conserved complex named COP9 signalosome has emerged as an essential and versatile regulator of biological and pathological responses across species. Various components of COP9 signalosome, including CSN5 (also named JAB1), play critical roles in a wide array of developmental process. Using genetically engineered mouse models, our laboratory has recently identified CSN5/JAB1 as an essential regulator of skeletal development, in part through negatively regulating BMP signaling. BMP signaling is important for fracture healing and bone regeneration. BMPs have been used for treating acute fractures and for improving the success of spinal fusions. Therefore, harnessing the CSN5/JAB1-mediated inhibition of BMP signaling might be a novel strategy to improve the efficacy of BMP treatment and to reduce medical costs in the future. Furthermore, the up-regulation of COP9 signalosome has been associated with various cancers, including osteosarcoma. Thus, the COP9 signalosome can also be a valid target for treating osteosarcoma and other tumors.