Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway
Rab21 is a GTPase protein that is functional in intracellular trafficking and involved in the pathologies of many diseases, such as Alzheimer’s disease (AD), glioma, cancer, etc. Our previous work has reported its interaction with the catalytic subunit of gamma-secretase, PS1, and it regulates the a...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/3/1131 |
| _version_ | 1797487587747692544 |
|---|---|
| author | Pinduo Liu Anping Wu Hui Li Jun Zhang Junjun Ni Zhenzhen Quan Hong Qing |
| author_facet | Pinduo Liu Anping Wu Hui Li Jun Zhang Junjun Ni Zhenzhen Quan Hong Qing |
| author_sort | Pinduo Liu |
| collection | DOAJ |
| description | Rab21 is a GTPase protein that is functional in intracellular trafficking and involved in the pathologies of many diseases, such as Alzheimer’s disease (AD), glioma, cancer, etc. Our previous work has reported its interaction with the catalytic subunit of gamma-secretase, PS1, and it regulates the activity of PS1 via transferring it from the early endosome to the late endosome/lysosome. However, it is still unknown how Rab21 protein itself is regulated. This work revealed that Rab21 protein, either endogenously or exogenously, can be degraded by the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. It is further observed that the ubiquitinated Rab21 is increased, but the total protein is unchanged in AD model mice. We further observed that overexpression of Rab21 leads to increased expression of a series of genes involved in the autophagy-lysosome pathway. We speculated that even though the ubiquitinated Rab21 is increased due to the impaired proteasome function in the AD model, the autophagy-lysosome pathway functions in parallel to degrade Rab21 to keep its protein level in homeostasis. In conclusion, understanding the characters of Rab21 protein itself help explore its potential as a target for therapeutic strategy in diseases. |
| first_indexed | 2024-03-09T23:50:48Z |
| format | Article |
| id | doaj.art-88952f8bbda2437fb2731c40fbb75f2c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:50:48Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-88952f8bbda2437fb2731c40fbb75f2c2023-11-23T16:35:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233113110.3390/ijms23031131Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome PathwayPinduo Liu0Anping Wu1Hui Li2Jun Zhang3Junjun Ni4Zhenzhen Quan5Hong Qing6Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, ChinaKey Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, ChinaKey Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, ChinaKey Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, ChinaKey Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, ChinaKey Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, ChinaKey Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, ChinaRab21 is a GTPase protein that is functional in intracellular trafficking and involved in the pathologies of many diseases, such as Alzheimer’s disease (AD), glioma, cancer, etc. Our previous work has reported its interaction with the catalytic subunit of gamma-secretase, PS1, and it regulates the activity of PS1 via transferring it from the early endosome to the late endosome/lysosome. However, it is still unknown how Rab21 protein itself is regulated. This work revealed that Rab21 protein, either endogenously or exogenously, can be degraded by the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. It is further observed that the ubiquitinated Rab21 is increased, but the total protein is unchanged in AD model mice. We further observed that overexpression of Rab21 leads to increased expression of a series of genes involved in the autophagy-lysosome pathway. We speculated that even though the ubiquitinated Rab21 is increased due to the impaired proteasome function in the AD model, the autophagy-lysosome pathway functions in parallel to degrade Rab21 to keep its protein level in homeostasis. In conclusion, understanding the characters of Rab21 protein itself help explore its potential as a target for therapeutic strategy in diseases.https://www.mdpi.com/1422-0067/23/3/1131Rab21 proteinubiquitin-proteasome pathwayautophagy-lysosome pathway |
| spellingShingle | Pinduo Liu Anping Wu Hui Li Jun Zhang Junjun Ni Zhenzhen Quan Hong Qing Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway International Journal of Molecular Sciences Rab21 protein ubiquitin-proteasome pathway autophagy-lysosome pathway |
| title | Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway |
| title_full | Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway |
| title_fullStr | Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway |
| title_full_unstemmed | Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway |
| title_short | Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway |
| title_sort | rab21 protein is degraded by both the ubiquitin proteasome pathway and the autophagy lysosome pathway |
| topic | Rab21 protein ubiquitin-proteasome pathway autophagy-lysosome pathway |
| url | https://www.mdpi.com/1422-0067/23/3/1131 |
| work_keys_str_mv | AT pinduoliu rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT anpingwu rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT huili rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT junzhang rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT junjunni rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT zhenzhenquan rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT hongqing rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway |