CDK4/6 Regulate Lysosome Biogenesis Through TFEB/TFE3

author:	Yin Q, Jian Y, Xu M, Huang X, Wang N, Liu Z, Li Q, Li J, Zhou H, Xu L, Wang Y, Yang C
Abstract:	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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PubYear:	2020
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Unit code:	152453
Publication name:	Journal of Cell Biology
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Paper source:	https://rupress.org/jcb/article/219/8/e201911036/151944/CDK4-6-regulate-lysosome-biogenesis-through-TFEB
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