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Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2

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...

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Autores principales: Xing, Yushu, Ba-tu, Jirimu, Dong, Chongyang, Cao, Xiaodong, Li, Bing, Jia, Xin, Juan, Yu, Lv, Xiaojie, Zhang, Huiwen, Qin, Na, Han, Wuri, Wang, Dongfeng, Qi, Xiao, Wang, Yutong, Hao, Xulu, Zhang, Shuang, Du, Xiaoli, Wang, Huanyun, Wang, Minjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687032/
https://www.ncbi.nlm.nih.gov/pubmed/38030604
http://dx.doi.org/10.1038/s41419-023-06304-y
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author Xing, Yushu
Ba-tu, Jirimu
Dong, Chongyang
Cao, Xiaodong
Li, Bing
Jia, Xin
Juan, Yu
Lv, Xiaojie
Zhang, Huiwen
Qin, Na
Han, Wuri
Wang, Dongfeng
Qi, Xiao
Wang, Yutong
Hao, Xulu
Zhang, Shuang
Du, Xiaoli
Wang, Huanyun
Wang, Minjie
author_facet Xing, Yushu
Ba-tu, Jirimu
Dong, Chongyang
Cao, Xiaodong
Li, Bing
Jia, Xin
Juan, Yu
Lv, Xiaojie
Zhang, Huiwen
Qin, Na
Han, Wuri
Wang, Dongfeng
Qi, Xiao
Wang, Yutong
Hao, Xulu
Zhang, Shuang
Du, Xiaoli
Wang, Huanyun
Wang, Minjie
author_sort Xing, Yushu
collection PubMed
description 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.
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spelling pubmed-106870322023-11-30 Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2 Xing, Yushu Ba-tu, Jirimu Dong, Chongyang Cao, Xiaodong Li, Bing Jia, Xin Juan, Yu Lv, Xiaojie Zhang, Huiwen Qin, Na Han, Wuri Wang, Dongfeng Qi, Xiao Wang, Yutong Hao, Xulu Zhang, Shuang Du, Xiaoli Wang, Huanyun Wang, Minjie Cell Death Dis Article 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. Nature Publishing Group UK 2023-11-29 /pmc/articles/PMC10687032/ /pubmed/38030604 http://dx.doi.org/10.1038/s41419-023-06304-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xing, Yushu
Ba-tu, Jirimu
Dong, Chongyang
Cao, Xiaodong
Li, Bing
Jia, Xin
Juan, Yu
Lv, Xiaojie
Zhang, Huiwen
Qin, Na
Han, Wuri
Wang, Dongfeng
Qi, Xiao
Wang, Yutong
Hao, Xulu
Zhang, Shuang
Du, Xiaoli
Wang, Huanyun
Wang, Minjie
Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2
title Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2
title_full Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2
title_fullStr Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2
title_full_unstemmed Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2
title_short Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2
title_sort phosphorylation of usp27x by gsk3β maintains the stability and oncogenic functions of cbx2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687032/
https://www.ncbi.nlm.nih.gov/pubmed/38030604
http://dx.doi.org/10.1038/s41419-023-06304-y
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