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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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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. |
format | Online Article Text |
id | pubmed-7401801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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