{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T16:59:24Z","timestamp":1778864364588,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92049102, 82071395, 31860270 &82001167"],"award-info":[{"award-number":["92049102, 82071395, 31860270 &82001167"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key R&amp;D Program of China","award":["2017YFE0117000, 2018YFC1312302-3"],"award-info":[{"award-number":["2017YFE0117000, 2018YFC1312302-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rab21 is a GTPase protein that is functional in intracellular trafficking and involved in the pathologies of many diseases, such as Alzheimer\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms23031131","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T22:51:06Z","timestamp":1642719066000},"page":"1131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway"],"prefix":"10.3390","volume":"23","author":[{"given":"Pinduo","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anping","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjun","family":"Ni","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhen","family":"Quan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Qing","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"ref_1","first-page":"bio045336","article-title":"RAB21 interacts with TMED10 and modulates its localization and abundance","volume":"8","author":"Normandin","year":"2019","journal-title":"Biol. 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