Translation Inhibitors Activate Autophagy Master Regulators TFEB and TFE3

The autophagy-lysosome pathway is a major protein degradation pathway stimulated by multiple cellular stresses, including nutrient or growth factor deprivation, hypoxia, misfolded proteins, damaged organelles, and intracellular pathogens. Recent studies have revealed that transcription factor EB (TF...

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Autores principales:	Thao Thi Dang, Sung Hoon Back
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	autophagy-lysosome pathway TFEB TFEB nuclear translocation mTOR calcineurin ribosome Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/f36e7439f509445291986f1e3643e03d
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spelling	oai:doaj.org-article:f36e7439f509445291986f1e3643e03d2021-11-11T17:28:18ZTranslation Inhibitors Activate Autophagy Master Regulators TFEB and TFE310.3390/ijms2221120831422-00671661-6596https://doaj.org/article/f36e7439f509445291986f1e3643e03d2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12083https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The autophagy-lysosome pathway is a major protein degradation pathway stimulated by multiple cellular stresses, including nutrient or growth factor deprivation, hypoxia, misfolded proteins, damaged organelles, and intracellular pathogens. Recent studies have revealed that transcription factor EB (TFEB) and transcription factor E3 (TFE3) play a pivotal role in the biogenesis and functions of autophagosome and lysosome. Here we report that three translation inhibitors (cycloheximide, lactimidomycin, and rocaglamide A) can facilitate the nuclear translocation of TFEB/TFE3 via dephosphorylation and 14-3-3 dissociation. In addition, the inhibitor-mediated TFEB/TFE3 nuclear translocation significantly increases the transcriptional expression of their downstream genes involved in the biogenesis and function of autophagosome and lysosome. Furthermore, we demonstrated that translation inhibition increased autophagosome biogenesis but impaired the degradative autolysosome formation because of lysosomal dysfunction. These results highlight the previously unrecognized function of the translation inhibitors as activators of TFEB/TFE3, suggesting a novel biological role of translation inhibition in autophagy regulation.Thao Thi DangSung Hoon BackMDPI AGarticleautophagy-lysosome pathwayTFEBTFEB nuclear translocationmTORcalcineurinribosomeBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12083, p 12083 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autophagy-lysosome pathway TFEB TFEB nuclear translocation mTOR calcineurin ribosome Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	autophagy-lysosome pathway TFEB TFEB nuclear translocation mTOR calcineurin ribosome Biology (General) QH301-705.5 Chemistry QD1-999 Thao Thi Dang Sung Hoon Back Translation Inhibitors Activate Autophagy Master Regulators TFEB and TFE3
description	The autophagy-lysosome pathway is a major protein degradation pathway stimulated by multiple cellular stresses, including nutrient or growth factor deprivation, hypoxia, misfolded proteins, damaged organelles, and intracellular pathogens. Recent studies have revealed that transcription factor EB (TFEB) and transcription factor E3 (TFE3) play a pivotal role in the biogenesis and functions of autophagosome and lysosome. Here we report that three translation inhibitors (cycloheximide, lactimidomycin, and rocaglamide A) can facilitate the nuclear translocation of TFEB/TFE3 via dephosphorylation and 14-3-3 dissociation. In addition, the inhibitor-mediated TFEB/TFE3 nuclear translocation significantly increases the transcriptional expression of their downstream genes involved in the biogenesis and function of autophagosome and lysosome. Furthermore, we demonstrated that translation inhibition increased autophagosome biogenesis but impaired the degradative autolysosome formation because of lysosomal dysfunction. These results highlight the previously unrecognized function of the translation inhibitors as activators of TFEB/TFE3, suggesting a novel biological role of translation inhibition in autophagy regulation.
format	article
author	Thao Thi Dang Sung Hoon Back
author_facet	Thao Thi Dang Sung Hoon Back
author_sort	Thao Thi Dang
title	Translation Inhibitors Activate Autophagy Master Regulators TFEB and TFE3
title_short	Translation Inhibitors Activate Autophagy Master Regulators TFEB and TFE3
title_full	Translation Inhibitors Activate Autophagy Master Regulators TFEB and TFE3
title_fullStr	Translation Inhibitors Activate Autophagy Master Regulators TFEB and TFE3
title_full_unstemmed	Translation Inhibitors Activate Autophagy Master Regulators TFEB and TFE3
title_sort	translation inhibitors activate autophagy master regulators tfeb and tfe3
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f36e7439f509445291986f1e3643e03d
work_keys_str_mv	AT thaothidang translationinhibitorsactivateautophagymasterregulatorstfebandtfe3 AT sunghoonback translationinhibitorsactivateautophagymasterregulatorstfebandtfe3
_version_	1718432095513083904

Translation Inhibitors Activate Autophagy Master Regulators TFEB and TFE3

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