The role of ubiquitination in tumorigenesis and targeted drug discovery

作     者：Lu Deng Tong Meng Lei Chen Wenyi Wei Ping Wang Lu Deng;Tong Meng;Lei Chen;Wenyi Wei;Ping Wang

作者机构：College of Animal Science and TechnologyNorthwest A&F UniversityYangling Shaanxi 712100China Division of SpineDepartment of OrthopedicsTongji Hospital Affiliated to Tongji University School of Medicine389 Xincun RoadShanghaiChina Division of Laboratory Safety and ServicesNorthwest A&F UniversityYangling Shaanxi 712100China Department of PathologyBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215USA Tongji University Cancer CenterShanghai Tenth People’s Hospital of Tongji UniversitySchool of MedicineTongji UniversityShanghai 200092China 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2020年第5卷第1期

页      面：2294-2321页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China(Nos.31801177,81702659,31830053,31920103007,81625019) the Science Technology Commission of Shanghai Municipality(No.18410722000) the Shanghai Sailing Program(No.18YF1419500) the Fundamental Research Funds for the Central Universities(No.22120180043) 

主　　题：metabolism ubiquitin targeted 

摘      要：Ubiquitination,an important type of protein posttranslational modification(PTM),plays a crucial role in controlling substrate degradation and subsequently mediates the“quantityand“qualityof various proteins,serving to ensure cell homeostasis and guarantee life *** regulation of ubiquitination is multifaceted and works not only at the transcriptional and posttranslational levels(phosphorylation,acetylation,methylation,etc.)but also at the protein level(activators or repressors).When regulatory mechanisms are aberrant,the altered biological processes may subsequently induce serious human diseases,especially various types of *** tumorigenesis,the altered biological processes involve tumor metabolism,the immunological tumor microenvironment(TME),cancer stem cell(CSC)stemness and so *** regard to tumor metabolism,the ubiquitination of some key proteins such as RagA,mTOR,PTEN,AKT,c-Myc and P53 significantly regulates the activity of the mTORC1,AMPK and PTEN-AKT signaling *** addition,ubiquitination in the TLR,RLR and STING-dependent signaling pathways also modulates the ***,the ubiquitination of core stem cell regulator triplets(Nanog,Oct4 and Sox2)and members of the Wnt and Hippo-YAP signaling pathways participates in the maintenance of CSC *** on the altered components,including the proteasome,E3 ligases,E1,E2 and deubiquitinases(DUBs),many molecular targeted drugs have been developed to combat *** them,small molecule inhibitors targeting the proteasome,such as bortezomib,carfilzomib,oprozomib and ixazomib,have achieved tangible *** addition,MLN7243 and MLN4924(targeting the E1 enzyme),Leucettamol A and CC0651(targeting the E2 enzyme),nutlin and MI‐219(targeting the E3 enzyme),and compounds G5 and F6(targeting DUB activity)have also shown potential in preclinical cancer *** this review,we summarize the latest progress in understanding the substrates for ubiquitination and their special functions