The role of E3 ubiquitin ligases in bone homeostasis and related diseases

Dong，Yuechao; Chen，Yangshan; Ma，Guixing; Cao，Huiling

2023

10.1016/j.apsb.2023.06.016

Acta Pharmaceutica Sinica B   Impact Factor & Quartile

2211-3835

2211-3843

The ubiquitin–proteasome system (UPS) dedicates to degrade intracellular proteins to modulate demic homeostasis and functions of organisms. These enzymatic cascades mark and modifies target proteins diversly through covalently binding ubiquitin molecules. In the UPS, E3 ubiquitin ligases are the crucial constituents by the advantage of recognizing and presenting proteins to proteasomes for proteolysis. As the major regulators of protein homeostasis, E3 ligases are indispensable to proper cell manners in diverse systems, and they are well described in physiological bone growth and bone metabolism. Pathologically, classic bone-related diseases such as metabolic bone diseases, arthritis, bone neoplasms and bone metastasis of the tumor, etc., were also depicted in a UPS-dependent manner. Therefore, skeletal system is versatilely regulated by UPS and it is worthy to summarize the underlying mechanism. Furthermore, based on the current status of treatment, normal or pathological osteogenesis and tumorigenesis elaborated in this review highlight the clinical significance of UPS research. As a strategy possibly remedies the limitations of UPS treatment, emerging PROTAC was described comprehensively to illustrate its potential in clinical application. Altogether, the purpose of this review aims to provide more evidence for exploiting novel therapeutic strategies based on UPS for bone associated diseases.

Bone resorption Chondrocyte E3 ubiquitin ligase Osteoblast Osteoclast Osteogenesis PROTAC UPS

English

First ; Corresponding

2-s2.0-85168432898

Scopus

Department of Biochemistry,School of Medicine,Southern University of Science and Technology,Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research,Key University Laboratory of Metabolism and Health of Guangdong,Shenzhen,518055,China

Dong，Yuechao,Chen，Yangshan,Ma，Guixing,et al. The role of E3 ubiquitin ligases in bone homeostasis and related diseases[J]. Acta Pharmaceutica Sinica B,2023.

Dong，Yuechao,Chen，Yangshan,Ma，Guixing,&Cao，Huiling.(2023).The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta Pharmaceutica Sinica B.

Dong，Yuechao,et al."The role of E3 ubiquitin ligases in bone homeostasis and related diseases".Acta Pharmaceutica Sinica B (2023).