CDK4/6 regulate lysosome biogenesis through TFEB/TFE3

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 c...

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Veröffentlicht in:The Journal of cell biology 2020-08, Vol.219 (8)
Hauptverfasser: Yin, Qiuyuan, Jian, Youli, Xu, Meng, Huang, Xiahe, Wang, Niya, Liu, Zhifang, Li, Qian, Li, Jinglin, Zhou, Hejiang, Xu, Lin, Wang, Yingchun, Yang, Chonglin
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container_issue 8
container_start_page
container_title The Journal of cell biology
container_volume 219
creator Yin, Qiuyuan
Jian, Youli
Xu, Meng
Huang, Xiahe
Wang, Niya
Liu, Zhifang
Li, Qian
Li, Jinglin
Zhou, Hejiang
Xu, Lin
Wang, Yingchun
Yang, Chonglin
description 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.
doi_str_mv 10.1083/jcb.201911036
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subjects Active Transport, Cell Nucleus
Autophagy
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism
Biochemistry
Cell Cycle
Cell Nucleus - enzymology
Cell Nucleus - genetics
Cell Proliferation
Cyclin D1 - metabolism
Cyclin-Dependent Kinase 4 - genetics
Cyclin-Dependent Kinase 4 - metabolism
Cyclin-Dependent Kinase 6 - genetics
Cyclin-Dependent Kinase 6 - metabolism
HCT116 Cells
HeLa Cells
Hep G2 Cells
Humans
Lysosomes - enzymology
Lysosomes - genetics
Organelle Biogenesis
Organelles
Phosphorylation
Proteolysis
Signal Transduction
title CDK4/6 regulate lysosome biogenesis through TFEB/TFE3
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