2. Academic Validation
  3. Nlp promotes autophagy through facilitating the interaction of Rab7 and FYCO1

Nlp promotes autophagy through facilitating the interaction of Rab7 and FYCO1

  • Signal Transduct Target Ther. 2021 Apr 16;6(1):152. doi: 10.1038/s41392-021-00543-1.
Wenchang Xiao  # 1 2,  Danna Yeerken  # 3,  Jia Li 1,  Zhangfu Li 4,  Lanfang Jiang 1,  Dan Li 1,  Ming Fu 1,  Liying Ma 1,  Yongmei Song 1,  Weimin Zhang 5 6,  Qimin Zhan 7 8 9 10
Affiliations

Affiliations

  • 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 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China. wmzhang411@163.com.
  • 6 Research Unit of Molecular Cancer Research, Chinese Academy of Medical Sciences, Beijing, China. wmzhang411@163.com.
  • 7 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. zhanqimin@bjmu.edu.cn.
  • 8 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China. zhanqimin@bjmu.edu.cn.
  • 9 Research Unit of Molecular Cancer Research, Chinese Academy of Medical Sciences, Beijing, China. zhanqimin@bjmu.edu.cn.
  • 10 Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China. zhanqimin@bjmu.edu.cn.
  • # Contributed equally.
PMID: 33859171 DOI: 10.1038/s41392-021-00543-1
Abstract

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 (Nlp), a well-characterized centrosomal associated protein, was able to modulate autophagosome transport and facilitate Autophagy. During Autophagy, Nlp colocalized with autophagosomes and physically interacted with autophagosome marker LC3, autophagosome sorting protein Rab7 and its downstream effector FYCO1. Interestingly, Nlp enhanced the interaction between Rab7 and FYCO1, 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 Nlp is also a new regulator of Autophagy, which promotes the interaction of Rab7 and FYCO1 and facilitates the formation of autophagolysosome.

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