信号肽-CUB-表皮生长因子样结构域蛋白家族作为辅助受体/配体参与胚胎发育和疾病发生  

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

作　　者：汪子杰 田智慧[2,3] 吴家媛 Wang Zijie;Tian Zhihui;Wu Jiayuan(Stomatological Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China;Department of Stomatology,Nanfang Hospital of Southern Medical University,Guangzhou 510000,Guangdong Province,China;School of Stomatology,Southern Medical University,Guangzhou 510000,Guangdong Province,China)

机构地区：[1]遵义医科大学附属口腔医院,贵州省遵义市563000 [2]南方医科大学南方医院口腔科,广东省广州市510000 [3]南方医科大学口腔医学院,广东省广州市510000

出　　处：《中国组织工程研究》2022年第32期5209-5216,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81460102),项目负责人:吴家媛;遵义市优秀青年科技创新人才培养项目(遵优青科[2018]8号),项目负责人:吴家媛;遵义医科大学附属口腔医院口腔感染性与恶性疾病的病因与防治团队项目[遵义市科合HZ字(2020)293号],项目负责人:吴家媛;贵州省卫生健康委科学技术基金项目(gzwjkj2020-1-163),项目负责人:吴家媛;广东省自然科学基金面上项目(2021A515011656),项目负责人:田智慧;南方医科大学南方医院院长基金面上项目(81772873),项目负责人:田智慧。

摘　　要：背景:信号肽-CUB-表皮生长因子样结构域蛋白(signal peptide-CUB-EGF-like domain-containing protein,SCUBE)可作为辅助受体和/或配体激活骨形态发生蛋白、血管内皮生长因子、转化生长因子β和刺猬因子等信号通路,在多种生理和病理过程中扮演着重要的角色。目的:综述国内外相关文献,总结SCUBE家族成员的结构与功能,以及在胚胎发育和疾病发生方面作用的研究进展。方法:第一作者应用计算机检索2000-2021年期间收录在PubMed和CNKI数据库的相关文章,英文检索词为“SCUBE,EGF family,structure and function,co-receptor,signaling pathways,embryonic development,disease,mechanism,tumor,protein,gene”,中文检索词为“SCUBE,表皮生长因子家族,结构功能,辅助受体,信号通路,胚胎发育,疾病,机制,肿瘤,蛋白,基因”。最终选择68篇文献进行综述。结果与结论:①SCUBE家族包括SCUBE1,SCUBE2,SCUBE3,家族成员共同拥有5个相似的结构域,包括1个氨基端的信号肽序列,9个串联排列的表皮生长因子样重复序列,1个氨基糖基化间隔区,3个富含半胱氨酸的结构域和1个羧基端的CUB样结构域;②SCUBE家族成员可作为辅助受体和/或配体,通过其特殊的CUB样结构域结合激活包括骨形态发生蛋白、转化生长因子β和血管内皮细胞生长因子在内的多条信号通路并产生相应的生物学效应;③SCUBE家族成员广泛表达于多种组织和器官,在脊椎动物胚胎发育过程中有着动态的表达模式;④SCUBE家族与疾病发生密切相关,可作为骨和牙齿发育异常、血管异常增生、自身免疫疾病和肿瘤等疾病的关键治疗靶点;⑤SCUBE家族成员在胚胎发育和疾病发生方面扮演着重要的角色,不仅可以作为疾病的治疗靶点,未来在组织工程领域再生也有着广泛的应用前景,但其具体功能和机制仍有待研究者们进一步深入研究。BACKG ROUND: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,transfo rming 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,corecepto r,signaling pathways,embryonic development,disease,mechanis m,tumor,protein,gene" in English and Chinese,respectively.Acco rding to the inclusion crite ria,68 articles were selected for review.RESULTS AND CONCLUSION:The SCUBE family includes three independent membe rs,SCUBE1,SCUBE2,and SCUBE3.SCUBE family membe rs 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 car boxy-terminal CUB-like domain.SCUBE family members can act as co receptors and/or ligands,binding thro ugh their special CUB-like domains to activate multiple signaling pathways including bone morphogenetic protein,transforming growth factor β and vascular endothelial growth fa ctor 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 ve rtebrate 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 dys plasia,vascular dysplasia,autoimmune diseases and tumo rs.SCUBE family membe rs play an important role in embryonic development and disease

关 键 词：SCUBE 表皮生长因子家族 结构功能 辅助受体 信号通路 胚胎发育 疾病 机制 肿瘤 蛋白 基因 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学]