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Phosphorylation of OTUB1 at Tyr 26 stabilizes the mTORC1 component, Raptor

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Author(s)
Seung Un SeoSeon Min WooMin Wook KimEun-Woo LeeKyoung-Jin MinTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Cell Death Differ
Issued Date
2023
Volume
30
Issue
1
Abstract
Raptor plays a critical role in mTORC1 signaling. High expression of Raptor is associated with resistance of cancer cells to PI3K/mTOR inhibitors. Here, we found that OTUB1-stabilized Raptor in a non-canonical manner. Using biochemical assays, we found that the tyrosine 26 residue (Y26) of OTUB1 played a critical role in the interaction between OTUB1 and Raptor. Furthermore, non-receptor tyrosine kinases (Src and SRMS kinases) induced phosphorylation of OTUB1 at Y26, which stabilized Raptor. Interestingly, phosphorylation of OTUB1 at Y26 did not affect the stability of other OTUB1-targeted substrates. However, dephosphorylation of OTUB1 destabilized Raptor and sensitized cancer cells to anti-cancer drugs via mitochondrial reactive oxygen species-mediated mitochondrial dysfunction. Furthermore, we detected high levels of phospho-OTUB1 and Raptor in samples of patients with renal clear carcinoma. Our results suggested that regulation of OTUB1 phosphorylation may be an effective and selective therapeutic target for treating cancers via down-regulation of Raptor.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
1476-5403
Source
https://www.nature.com/articles/s41418-022-01047-3
DOI
10.1038/s41418-022-01047-3
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44728
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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