2022, Vol. 26 ›› Issue (32): 5209-5216

Signal peptide-CUB-epidermal growth factor-like domain protein family as coreceptors/ligands is involved in embryonic development and disease development

Wang Zijie1, Tian Zhihui2, 3, Wu Jiayuan1   

Abstract: BACKGROUND: Signal peptide-CUB-EGF-like domain-containing protein (SCUBE) can act as a coreceptor and/or a ligand to activate signaling pathways, such as bone morphogenetic protein, vascular endothelial growth factor, transforming growth factor β, and hedgehog, and plays an important role in a variety of physiological and pathological processes
OBJECTIVE: To review relevant literature worldwide and summarize the research progress in the structure and function of SCUBE family, as well as their roles in embryonic development and disease occurrence.
METHODS: The first author used a computer to search for related articles included in PubMed and CNKI databases from 2000 to 2021. The search terms were “SCUBE, EGF family, structure and function, coreceptor, signaling pathways, embryonic development, disease, mechanism, tumor, protein, gene” in English and Chinese, respectively. According to the inclusion criteria, 68 articles were selected for review.
RESULTS AND CONCLUSION: The SCUBE family includes three independent members, SCUBE1, SCUBE2, and SCUBE3. SCUBE family members share five similar domains, including one amino-terminal signal peptide sequence, nine tandemly arranged epidermal growth factor-like repeats, one amino glycosylation spacer, three cysteine-rich domains, and one carboxy-terminal CUB-like domain. SCUBE family members can act as coreceptors and/or ligands, binding through their special CUB-like domains to activate multiple signaling pathways including bone morphogenetic protein, transforming growth factor β and vascular endothelial growth factor and produce corresponding biological effects. SCUBE family members are widely expressed in a variety of tissues and organs, and have a dynamic expression pattern during vertebrate embryonic development. The SCUBE family is closely related to the occurrence of diseases, and can be used as key therapeutic targets for diseases such as bone and tooth dysplasia, vascular dysplasia, autoimmune diseases and tumors. SCUBE family members play an important role in embryonic development and disease occurrence. They can not only be used as therapeutic targets for diseases, but also have broad application prospects in the field of tissue engineering regeneration in the future. However, their specific functions and mechanisms still need to be further studied.
Key words: SCUBE, epidermal growth factor family, structure and function, coreceptor, signaling pathway, embryonic development, disease, mechanism, tumor, protein, gene