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典型文献
AKR1C1 connects autophagy and oxidative stress by interacting with SQSTM1 in a catalytic-independent manner
文献摘要:
Targeting autophagy might be a promising anticancer strategy;however,the dual roles of autophagy in cancer development and malignancy remain unclear.NSCLC(non-small cell lung cancer)cells harbour high levels of SQSTM1(sequestosome 1),the autophagy receptor that is critical for the dual roles of autophagy.Therefore,mechanistic insights into SQSTM1 modulation may point towards better approaches to treat NSCLC.Herein,we used multiple autophagy flux models and autophagy readouts to show that aldo-keto reductase family 1 member C1(AKR1C1),which is highly expressed in NSCLC,promotes autophagy by directly binding to SQSTM1 in a catalytic-independent manner.This interaction may be strengthened by reactive oxygen species(ROS),important autophagy inducers.Further mechanistic research demonstrated that AKR1C1 interacts with SQSTM1 to augment SQSTM1 oligomerization,contributing to the SQSTM1 affinity for binding cargo.Collectively,our data reveal a catalytic-independent role of AKR1C1 for interacting with SQSTM1 and promoting autophagy.All these findings not only reveal a novel functional role of AKR1C1 in the autophagy process but also indicate that modulation of the AKR1C1-SQSTM1 interaction may be a new strategy for targeting autophagy.
文献关键词:
作者姓名:
Lin-lin Chang;Yue-kang Li;Chen-xi Zhao;Chen-ming Zeng;Fu-jing Ge;Jia-min Du;Wen-zhou Zhang;Pei-hua Lu;Qiao-jun He;Hong Zhu;Bo Yang
作者机构:
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;Department of Pharmacy,Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Zhengzhou 450000,China;Department of Medical Oncology,Wuxi People's Hospital of Nanjing Medical University,Wuxi 214023,China
引用格式:
[1]Lin-lin Chang;Yue-kang Li;Chen-xi Zhao;Chen-ming Zeng;Fu-jing Ge;Jia-min Du;Wen-zhou Zhang;Pei-hua Lu;Qiao-jun He;Hong Zhu;Bo Yang-.AKR1C1 connects autophagy and oxidative stress by interacting with SQSTM1 in a catalytic-independent manner)[J].中国药理学报(英文版),2022(03):703-711
A类:
readouts,aldo
B类:
AKR1C1,connects,autophagy,oxidative,stress,by,interacting,SQSTM1,catalytic,independent,manner,Targeting,might,promising,anticancer,strategy,however,dual,roles,development,malignancy,remain,unclear,NSCLC,small,lung,cells,harbour,levels,sequestosome,receptor,that,critical,Therefore,mechanistic,insights,into,modulation,may,point,towards,better,approaches,treat,Herein,used,multiple,flux,models,show,keto,reductase,family,member,which,highly,expressed,promotes,directly,binding,This,interaction,strengthened,reactive,oxygen,species,ROS,important,inducers,Further,research,demonstrated,interacts,augment,oligomerization,contributing,affinity,cargo,Collectively,data,reveal,promoting,All,these,findings,not,only,novel,functional,process,also,indicate,new,targeting
AB值:
0.523004
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