Chaperone-assisted E3 ligase CHIP:A double agent in cancer  

作　　者：Sunny Kumar Malini Basu Mrinal K.Ghosh 

机构地区：[1]Cancer Biology and Inflammatory Disorder Division,Council of Scientific and Industrial Research-Indian Institute of Chemical Biology(CSIR-IICB),TRUE Campus,CN-6,SectoreV,Salt Lake,Kolkata-700091&4,Raja S.C.Mullick Road,Jadavpur,Kolkata 700032,India [2]Department of Microbiology,Dhruba Chand Halder College,Dakshin Barasat,South 24 Paraganas,West Bengal 743372,India

出　　处：《Genes & Diseases》2022年第6期1521-1555,共35页基因与疾病（英文）

基　　金：This work is jointly supported by the Department of Science and Technology(NanoMission:DST/NM/NT/2018/105(G);SERB:EMR/2017/000992);HCT-Focused Basic Research(FBR),(Sanction No.31-2(274)2020-21/Bud-II,dated-03.03.2021),CSIR,Govt.of India.

摘　　要：The carboxy-terminus of Hsp70-interacting protein(CHIP)is a ubiquitin ligase and co-chaperone belonging to Ubox family that plays a crucial role in the maintenance of cellular homeostasis by switching the equilibrium of the folding-refolding mechanism towards the proteasomal or lysosomal degradation pathway.It links molecular chaperones viz.HSC70,HSP70 and HSP90 with ubiquitin proteasome system(UPS),acting as a quality control system.CHIP contains charged domain in between N-terminal tetratricopeptide repeat(TPR)and C-terminal Ubox domain.TPR domain interacts with the aberrant client proteins via chaperones while Ubox domain facilitates the ubiquitin transfer to the client proteins for ubiquitination.Thus,CHIP is a classic molecule that executes ubiquitination for degradation of client proteins.Further,CHIP has been found to be indulged in cellular differentiation,proliferation,metastasis and tumorigenesis.Additionally,CHIP can play its dual role as a tumor suppressor as well as an oncogene in numerous malignancies,thus acting as a double agent.Here,in this review,we have reported almost all substrates of CHIP established till date and classified them according to the hallmarks of cancer.In addition,we discussed about its architectural alignment,tissue specific expression,sub-cellular localization,folding-refolding mechanisms of client proteins,E4 ligase activity,normal physiological roles,as well as involvement in various diseases and tumor biology.Further,we aim to discuss its importance in HSP90 inhibitors mediated cancer therapy.Thus,this report concludes that CHIP may be a promising and worthy drug target towards pharmaceutical industry for drug development.

关 键 词：Chaperones(HSC70/HSP70&HSP90) CHIP ONCOGENE Therapy Tumor suppressor Ubiquitin proteasome system(UPS) 

分 类 号：R730[医药卫生—肿瘤]