Dual function of the Leon/USP5 deubiquitinase in the ubiquitin-proteasome and autophagic pathways
ABSTRACTThe ubiquitin-proteasome system (UPS) and autophagy are highly conserved processes that maintain cellular health through the clearance of misfolded/aberrant proteins and damaged organelles. Ubiquitination is a crucial protein modification to regulate entry in these two pathways. However, the...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Autophagy Reports |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2023.2278299 |
| _version_ | 1797633043838533632 |
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| author | Yuchieh Jay Lin Guang-Chao Chen |
| author_facet | Yuchieh Jay Lin Guang-Chao Chen |
| author_sort | Yuchieh Jay Lin |
| collection | DOAJ |
| description | ABSTRACTThe ubiquitin-proteasome system (UPS) and autophagy are highly conserved processes that maintain cellular health through the clearance of misfolded/aberrant proteins and damaged organelles. Ubiquitination is a crucial protein modification to regulate entry in these two pathways. However, the function of deubiquitinases (DUBs) in the UPS and autophagy remains largely unclear. The Leon/USP5 deubiquitinase is essential for maintaining ubiquitin homeostasis and proteasome function. In our recent study, we found that Leon/USP5 depletion resulted in the induction of autophagosome formation and an enhancement of the autophagic flux. Additionally, a genetic analysis in Drosophila revealed that Leon overexpression suppressed Atg1-induced cell death. We further showed that Leon/USP5 interacts with the autophagy initiator Atg1/ULK1, regulating its levels and thus modulating autophagosome formation. These findings suggest that Leon/USP5 plays a dual role in regulation of UPS and autophagy.Abbreviations: Atg1: autophagy-related 1; Atg7: autophagy-related 7; DUB: deubiquitinase; ED: enzyme dead; PTM: post-translational modification; SQSTM1: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1; UPS: ubiquitin-proteasome system; USP5: ubiquitin-specific proteinase 5; WT: wild-type. |
| first_indexed | 2024-03-11T11:45:18Z |
| format | Article |
| id | doaj.art-1f8ba98c48394492a72aa263b004d2cd |
| institution | Directory Open Access Journal |
| issn | 2769-4127 |
| language | English |
| last_indexed | 2024-03-11T11:45:18Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj.art-1f8ba98c48394492a72aa263b004d2cd2023-11-09T12:28:54ZengTaylor & Francis GroupAutophagy Reports2769-41272023-12-012110.1080/27694127.2023.2278299Dual function of the Leon/USP5 deubiquitinase in the ubiquitin-proteasome and autophagic pathwaysYuchieh Jay Lin0Guang-Chao Chen1Institute of Biological Chemistry, Academia Sinica, Taipei 115, TaiwanInstitute of Biological Chemistry, Academia Sinica, Taipei 115, TaiwanABSTRACTThe ubiquitin-proteasome system (UPS) and autophagy are highly conserved processes that maintain cellular health through the clearance of misfolded/aberrant proteins and damaged organelles. Ubiquitination is a crucial protein modification to regulate entry in these two pathways. However, the function of deubiquitinases (DUBs) in the UPS and autophagy remains largely unclear. The Leon/USP5 deubiquitinase is essential for maintaining ubiquitin homeostasis and proteasome function. In our recent study, we found that Leon/USP5 depletion resulted in the induction of autophagosome formation and an enhancement of the autophagic flux. Additionally, a genetic analysis in Drosophila revealed that Leon overexpression suppressed Atg1-induced cell death. We further showed that Leon/USP5 interacts with the autophagy initiator Atg1/ULK1, regulating its levels and thus modulating autophagosome formation. These findings suggest that Leon/USP5 plays a dual role in regulation of UPS and autophagy.Abbreviations: Atg1: autophagy-related 1; Atg7: autophagy-related 7; DUB: deubiquitinase; ED: enzyme dead; PTM: post-translational modification; SQSTM1: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1; UPS: ubiquitin-proteasome system; USP5: ubiquitin-specific proteinase 5; WT: wild-type.https://www.tandfonline.com/doi/10.1080/27694127.2023.2278299Atg1/ULK1autophagydeubiquitinaseLeon/USP5Ref(2)P/SQSTM1 |
| spellingShingle | Yuchieh Jay Lin Guang-Chao Chen Dual function of the Leon/USP5 deubiquitinase in the ubiquitin-proteasome and autophagic pathways Autophagy Reports Atg1/ULK1 autophagy deubiquitinase Leon/USP5 Ref(2)P/SQSTM1 |
| title | Dual function of the Leon/USP5 deubiquitinase in the ubiquitin-proteasome and autophagic pathways |
| title_full | Dual function of the Leon/USP5 deubiquitinase in the ubiquitin-proteasome and autophagic pathways |
| title_fullStr | Dual function of the Leon/USP5 deubiquitinase in the ubiquitin-proteasome and autophagic pathways |
| title_full_unstemmed | Dual function of the Leon/USP5 deubiquitinase in the ubiquitin-proteasome and autophagic pathways |
| title_short | Dual function of the Leon/USP5 deubiquitinase in the ubiquitin-proteasome and autophagic pathways |
| title_sort | dual function of the leon usp5 deubiquitinase in the ubiquitin proteasome and autophagic pathways |
| topic | Atg1/ULK1 autophagy deubiquitinase Leon/USP5 Ref(2)P/SQSTM1 |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2023.2278299 |
| work_keys_str_mv | AT yuchiehjaylin dualfunctionoftheleonusp5deubiquitinaseintheubiquitinproteasomeandautophagicpathways AT guangchaochen dualfunctionoftheleonusp5deubiquitinaseintheubiquitinproteasomeandautophagicpathways |