期刊
SIGNAL TRANSDUCTION AND TARGETED THERAPY
卷 6, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41392-021-00543-1
关键词
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资金
- National Natural Science Foundation of China [81988101, 81802780, 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-5081]
- Science Foundation of Peking University Cancer Hospital [2020-8]
- Major Program of Shenzhen Bay Laboratory [S201101004]
- Guangdong Basic and Applied Basic Research Foundation [2019B030302012]
- Fund of San-ming Project of Medicine in Shenzhen [SZSM201812088]
Autophagy is a crucial pathway for maintaining intracellular homeostasis and preventing malignant transformation. The study reveals that Nlp, a centrosomal protein, is a novel regulator of autophagy that enhances the interaction between Rab7 and FYCO1, facilitating autophagolysosome formation and accelerating autophagic flux. Deficiency of Nlp leads to hepatic autophagic defects and increased incidence of liver cancer in mice.
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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