2. Academic Validation
  3. Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2

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

  • Cell Death Dis. 2023 Nov 29;14(11):782. doi: 10.1038/s41419-023-06304-y.
Yushu Xing 1 2,  Jirimu Ba-Tu 3,  Chongyang Dong 4,  Xiaodong Cao 1 2,  Bing Li 1,  Xin Jia 1,  Yu Juan 1,  Xiaojie Lv 1,  Huiwen Zhang 1,  Na Qin 5,  Wuri Han 5,  Dongfeng Wang 4,  Xiao Qi 1,  Yutong Wang 1,  Xulu Hao 4,  Shuang Zhang 4,  Xiaoli Du 6 7,  Huanyun Wang 8,  Minjie Wang 9
Affiliations

Affiliations

  • 1 College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
  • 2 The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
  • 3 Medical Innovation Center for Nationalities, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
  • 4 College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
  • 5 College of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
  • 6 College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China. 48121567@qq.com.
  • 7 The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China. 48121567@qq.com.
  • 8 College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China. whuanyun999@163.com.
  • 9 Medical Experimental Center of Basic Medical School, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China. wangminjienmg@163.com.
PMID: 38030604 DOI: 10.1038/s41419-023-06304-y
Abstract

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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