Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2
© 2023. The Author(s)..
Chromobox protein homolog 2 (CBX2) exerts a multifaceted impact on the progression of aggressive cancers. The proteasome-dependent pathway is crucial for modulating CBX2 regulation, while the specific regulatory roles and mechanisms of deubiquitinating enzymes targeting CBX2 remain poorly understood. Mass spectrometry analysis identified ubiquitin-specific peptidase 27X (USP27X) as a deubiquitinating enzyme that targets CBX2. Overexpression of USP27X significantly enhances CBX2 levels by promoting deubiquitination, while deficiency of USP27X leads to CBX2 degradation, thereby inhibiting tumorigenesis. Furthermore, it has been revealed that glycogen synthase kinase 3 beta (GSK3β) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 and leading to further stabilization of the CBX2 protein. Clinically, the co-expression of high levels of USP27X and CBX2 in breast cancer tissues is indicative of a poor prognosis for patients with this disease. These findings collectively underscore the critical regulatory role played by USP27X in modulating CBX2, thereby establishing the GSK3β-USP27X-CBX2 axis as a pivotal driver of malignant progression in breast cancer.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Cell death & disease - 14(2023), 11 vom: 29. Nov., Seite 782 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xing, Yushu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.12.2023 Date Revised 25.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41419-023-06304-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365217441 |
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| 100 | 1 | |a Xing, Yushu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2 |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 04.12.2023 | ||
| 500 | |a Date Revised 25.01.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Chromobox protein homolog 2 (CBX2) exerts a multifaceted impact on the progression of aggressive cancers. The proteasome-dependent pathway is crucial for modulating CBX2 regulation, while the specific regulatory roles and mechanisms of deubiquitinating enzymes targeting CBX2 remain poorly understood. Mass spectrometry analysis identified ubiquitin-specific peptidase 27X (USP27X) as a deubiquitinating enzyme that targets CBX2. Overexpression of USP27X significantly enhances CBX2 levels by promoting deubiquitination, while deficiency of USP27X leads to CBX2 degradation, thereby inhibiting tumorigenesis. Furthermore, it has been revealed that glycogen synthase kinase 3 beta (GSK3β) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 and leading to further stabilization of the CBX2 protein. Clinically, the co-expression of high levels of USP27X and CBX2 in breast cancer tissues is indicative of a poor prognosis for patients with this disease. These findings collectively underscore the critical regulatory role played by USP27X in modulating CBX2, thereby establishing the GSK3β-USP27X-CBX2 axis as a pivotal driver of malignant progression in breast cancer | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Ba-Tu, Jirimu |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Chongyang |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Xiaodong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Juan, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Xiaojie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Huiwen |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Wuri |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Dongfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yutong |e verfasserin |4 aut | |
| 700 | 1 | |a Hao, Xulu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Xiaoli |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Huanyun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Minjie |e verfasserin |4 aut | |
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