TFEB
溶酶体
细胞生物学
自噬
生物
生物发生
细胞周期
亚细胞定位
内体
细胞器
细胞
生物化学
基因
酶
细胞凋亡
作者
Qiuyuan Yin,Youli Jian,Meng Xu,Xiahe Huang,Niya Wang,Zhifang Liu,Qian Li,Jinglin Li,Hejiang Zhou,Lin Xu,Yingchun Wang,Chonglin Yang
标识
DOI:10.1083/jcb.201911036
摘要
Lysosomes are degradation and signaling organelles that adapt their biogenesis to meet many different cellular demands; however, it is unknown how lysosomes change their numbers for cell division. Here, we report that the cyclin-dependent kinases CDK4/6 regulate lysosome biogenesis during the cell cycle. Chemical or genetic inactivation of CDK4/6 increases lysosomal numbers by activating the lysosome and autophagy transcription factors TFEB and TFE3. CDK4/6 interact with and phosphorylate TFEB/TFE3 in the nucleus, thereby inactivating them by promoting their shuttling to the cytoplasm. During the cell cycle, lysosome numbers increase in S and G2/M phases when cyclin D turnover diminishes CDK4/6 activity. These findings not only uncover the molecular events that direct the nuclear export of TFEB/TFE3, but also suggest a mechanism that controls lysosome biogenesis in the cell cycle. CDK4/6 inhibitors promote autophagy and lysosome-dependent degradation, which has important implications for the therapy of cancer and lysosome-related disorders.
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