CDK4/6 regulate lysosome biogenesis through TFEB/TFE3.
J Cell Biol
; 219(8)2020 08 03.
Article
en En
| MEDLINE
| ID: mdl-32662822
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biogénesis de Organelos
/
Núcleo Celular
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Quinasa 4 Dependiente de la Ciclina
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Quinasa 6 Dependiente de la Ciclina
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice
/
Lisosomas
Límite:
Humans
Idioma:
En
Revista:
J Cell Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
China