Cargando…
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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835697/ https://www.ncbi.nlm.nih.gov/pubmed/35163051 http://dx.doi.org/10.3390/ijms23031131 |
_version_ | 1784649495999414272 |
---|---|
author | Liu, Pinduo Wu, Anping Li, Hui Zhang, Jun Ni, Junjun Quan, Zhenzhen Qing, Hong |
author_facet | Liu, Pinduo Wu, Anping Li, Hui Zhang, Jun Ni, Junjun Quan, Zhenzhen Qing, Hong |
author_sort | Liu, Pinduo |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8835697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88356972022-02-12 Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway Liu, Pinduo Wu, Anping Li, Hui Zhang, Jun Ni, Junjun Quan, Zhenzhen Qing, Hong Int J Mol Sci Article 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. MDPI 2022-01-20 /pmc/articles/PMC8835697/ /pubmed/35163051 http://dx.doi.org/10.3390/ijms23031131 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Pinduo Wu, Anping Li, Hui Zhang, Jun Ni, Junjun Quan, Zhenzhen Qing, Hong Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the 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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835697/ https://www.ncbi.nlm.nih.gov/pubmed/35163051 http://dx.doi.org/10.3390/ijms23031131 |
work_keys_str_mv | AT liupinduo rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT wuanping rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT lihui rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT zhangjun rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT nijunjun rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT quanzhenzhen rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway AT qinghong rab21proteinisdegradedbyboththeubiquitinproteasomepathwayandtheautophagylysosomepathway |