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Translation Inhibitors Activate Autophagy Master Regulators TFEB and TFE3

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Abstract
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.
Author(s)
당 티 타오백승훈
Issued Date
2021
Type
Article
Keyword
autophagy-lysosome pathwayTFEBTFEB nuclear translocationmTORcalcineurinribosomeeIF4A helicasetranslation inhibitor
DOI
10.3390/ijms222112083
URI
https://oak.ulsan.ac.kr/handle/2021.oak/9584
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_f36e7439f509445291986f1e3643e03d&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Translation%20Inhibitors%20Activate%20Autophagy%20Master%20Regulators%20TFEB%20and%20TFE3&offset=0&pcAvailability=true
Publisher
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Location
스위스
Language
영어
ISSN
1422-0067
Citation Volume
22
Citation Number
21
Citation Start Page
12083
Citation End Page
12083
Appears in Collections:
Natural Science > Biological Sciences
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