Nip promotes autophagy through facilitating the interaction of Rab7 and FYCO1  

作　　者：Wenchang Xiao Danna Yeerken Jia Li Zhangfu Li Lanfang Jiang Dan Li Ming Fu Liying Ma Yongmei Song Weimin Zhang Qimin Zhan 

机构地区：[1]State Key Laboratory of Molecular Oncology,National Cancer center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China [2]Department of Biomedical Engineering,College of Life Science and Technology,Huazhong University of Science and Technology(HUST),Wuhan,China [3]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Laboratory of Molecular Oncology,Peking University Cancer Hospital&Institute,Beijing,China [4]Department of Hepato-Pancreato-Biliary Surgery,Peking University Shenzhen Hospital,Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center,Shenzhen,China [5]Research Unit of Molecular Cancer Research,Chinese Academy of Medical Sciences,Beijing,China [6]Institute of Cancer Research,Shenzhen Bay Laboratory,Shenzhen,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第5期1559-1572,共14页信号转导与靶向治疗（英文）

基　　金：This work was supported by the National Natural Science Foundation of China(81988101,81802780,and 81830086);Beijing Municipal Commission of Health and Family Planning Project(PXM2018_026279_000005);Beijing Nova Program(Z191100001119038);CAMS Innovation Fund for Medical Sciences(2019-I2M-5-081);Science Foundation of Peking University Cancer Hospital(2020-8);Funding by Major Program of Shenzhen Bay Laboratory(S201101004);Guangdong Basic and Applied Basic Research Foundation(2019B030302012);the Fund of"San-ming"Project of Medicine in Shenzhen(No.SZSM201812088).

摘　　要：Autophagy is the main degradation pathway to eliminate long-lived and aggregated proteins,aged or malfunctioning organelles,which is essential for the intracellular homeostasis and prevention of malignant transformation.Although the processes of autophagosome biogenesis have been well illuminated,the mechanism of autophagosome transport remains largely unclear.In this study,we demonstrated that the ninein-like protein(Nip),a well-characterized centrosomal associated protein,was able to modulate autophagosome transport and facilitate autophagy.During autophagy,Nip colocalized with autophagosomes and physically interacted with autophagosome marker LC3,autophagosome sorting protein Rab7 and its downstream effector FYCOl.Interestingly,Nip enhanced the interaction between Rab7 and FYC01,thus accelerated autophagic flux and the formation of autophagolysosomes.Furthermore,compared to the wild-type mice,NLP deficient mice treated with chemical agent DMBA were prone to increased incidence of hepatomegaly and liver cancer,which were tight associated with the hepatic autophagic defect.Taken together,our findings provide a new insight for the first time that the well-known centrosomal protein Nip is also a new regulator of autophagy,which promotes the interaction of Rab7 and FYC01 and facilitates the formation of autophagolysosome.

关 键 词：PREVENTION DMBA interaction 

分 类 号：R730[医药卫生—肿瘤]