The role of proteasomes in tumorigenesis  

作　　者：Xiangyi Zhou Ruqing Xu Yue Wu Li Zhou Tingxiu Xiang 

机构地区：[1]Department of Oncology,The First Affliated Hospital of Chongqing Medical University,Chongqing 400016,China [2]Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital,Chongqing 400030,China

出　　处：《Genes & Diseases》2024年第4期155-169,共15页基因与疾病（英文）

基　　金：supported by the National Natural Science Foundation of China(No.82172619);the Natural Science Foundation of Chongqing,China(No.CSTC2021jscx-gksb-No023);the Medical and Industrial Integration Project(China)(No.2022CDJYGRH-002).

摘　　要：Protein homeostasis is the basis of normal life activities,and the proteasomefamily plays an extremely important function in this process.The proteasome 2os is a concentric circle structure with twoαrings and twoβrings overlapped.The proteasome 2os can perform both ATP-dependent and non-ATP-dependent ubiquitination proteasome degradation by binding to various subunits(such as 19S,11S,and 200 PA),which is performed by its active subunitβ1,β2,andβ5.The proteasome can degrade misfolded,excess proteins tomaintain homeostasis.At the same time,it can be utilized by tumors to degrade over-proliferate and unwanted proteins to support their growth.Proteasomes can affect the development of tumors from several aspects including tumor signaling pathways such as NF-kB and p53,cell cycle,immune regulation,and drug resistance.Proteasome-encoding genes have been found to be overexpressed in a variety of tumors,providing a potential novel target for cancer therapy.In addition,proteasome inhibitors such as bortezomib,carfilzomib,and ixazomib have been put into clinical application as the first-line treatment of multiple myeloma.More and more studies have shown that it also has different therapeutic effects in other tumors such as hepatocellular carcinoma,non-small cell lung cancer,glioblastoma,and neuroblastoma.However,proteasome inhibitors are not much effective due to their tolerance and singleness in other tumors.Therefore,further studies on their mechanisms of action and drug interactions are needed to investigate their therapeutic potential.

关 键 词：BORTEZOMIB Cancer therapy IMMUNOPROTEASOME MULTIPLEMYELOMA Proteasome 20S Proteasome inhibitor Thymoproteasom 

分 类 号：R730.2[医药卫生—肿瘤]