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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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Autores principales: Yin, Qiuyuan, Jian, Youli, Xu, Meng, Huang, Xiahe, Wang, Niya, Liu, Zhifang, Li, Qian, Li, Jinglin, Zhou, Hejiang, Xu, Lin, Wang, Yingchun, Yang, Chonglin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401801/
https://www.ncbi.nlm.nih.gov/pubmed/32662822
http://dx.doi.org/10.1083/jcb.201911036
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author Yin, Qiuyuan
Jian, Youli
Xu, Meng
Huang, Xiahe
Wang, Niya
Liu, Zhifang
Li, Qian
Li, Jinglin
Zhou, Hejiang
Xu, Lin
Wang, Yingchun
Yang, Chonglin
author_facet Yin, Qiuyuan
Jian, Youli
Xu, Meng
Huang, Xiahe
Wang, Niya
Liu, Zhifang
Li, Qian
Li, Jinglin
Zhou, Hejiang
Xu, Lin
Wang, Yingchun
Yang, Chonglin
author_sort Yin, Qiuyuan
collection PubMed
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.
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spelling pubmed-74018012021-02-03 CDK4/6 regulate lysosome biogenesis through TFEB/TFE3 Yin, Qiuyuan Jian, Youli Xu, Meng Huang, Xiahe Wang, Niya Liu, Zhifang Li, Qian Li, Jinglin Zhou, Hejiang Xu, Lin Wang, Yingchun Yang, Chonglin J Cell Biol Article 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. Rockefeller University Press 2020-07-14 /pmc/articles/PMC7401801/ /pubmed/32662822 http://dx.doi.org/10.1083/jcb.201911036 Text en © 2020 Yin et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Yin, Qiuyuan
Jian, Youli
Xu, Meng
Huang, Xiahe
Wang, Niya
Liu, Zhifang
Li, Qian
Li, Jinglin
Zhou, Hejiang
Xu, Lin
Wang, Yingchun
Yang, Chonglin
CDK4/6 regulate lysosome biogenesis through TFEB/TFE3
title CDK4/6 regulate lysosome biogenesis through TFEB/TFE3
title_full CDK4/6 regulate lysosome biogenesis through TFEB/TFE3
title_fullStr CDK4/6 regulate lysosome biogenesis through TFEB/TFE3
title_full_unstemmed CDK4/6 regulate lysosome biogenesis through TFEB/TFE3
title_short CDK4/6 regulate lysosome biogenesis through TFEB/TFE3
title_sort cdk4/6 regulate lysosome biogenesis through tfeb/tfe3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401801/
https://www.ncbi.nlm.nih.gov/pubmed/32662822
http://dx.doi.org/10.1083/jcb.201911036
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