2. Academic Validation
  3. USP33 facilitates the ovarian cancer progression via deubiquitinating and stabilizing CBX2

USP33 facilitates the ovarian cancer progression via deubiquitinating and stabilizing CBX2

  • Oncogene. 2024 Oct;43(43):3170-3183. doi: 10.1038/s41388-024-03151-9.
Jiming Chen # 1,  Wulin Shan # 2 3,  Qiucheng Jia # 1,  Yao Chen # 3 4,  Wenjing Jiang 2 3,  Yuan Tian 2 3,  Xu Huang 2 3,  Xiaoyu Li 2 3,  Zengying Wang 3 4,  Bairong Xia 5 6 7
Affiliations

Affiliations

  • 1 Department of Gynecology, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.
  • 2 Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
  • 3 Department of Obstetrics and Gynecology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China.
  • 4 Bengbu Medical University, Bengbu, Anhui, China.
  • 5 Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. xiabairong@ustc.edu.cn.
  • 6 Department of Obstetrics and Gynecology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China. xiabairong@ustc.edu.cn.
  • 7 Bengbu Medical University, Bengbu, Anhui, China. xiabairong@ustc.edu.cn.
  • # Contributed equally.
PMID: 39256572 DOI: 10.1038/s41388-024-03151-9
Abstract

Post-translational modifications of proteins play a pivotal role in both the initiation and progression of ovarian Cancer. Despite the recognition of USP33 as a significant factor in various cancers, its specific function and underlying mechanisms in ovarian Cancer remain elusive. Proteomics and ubiquitinomics approaches were coupled to screen novel substrate proteins directly regulated by USP33. Our findings unveil that USP33 was observed to eliminate K27- and K48-linked ubiquitin chains from CBX2 at the K277 position. Notably, acetylation of CBX2 at K199, catalyzed by lysine acetyltransferase GCN5, was found to enhance its interaction with USP33, subsequently promoting further deubiquitination and stabilization. Functionally, our experiments demonstrate that USP33 significantly enhances ovarian Cancer proliferation and metastasis in a CBX2-dependent manner. Furthermore, analysis revealed a direct positive correlation between the expression levels of USP33 and CBX2 proteins in human specimens, with elevated levels being associated with reduced survival rates in ovarian Cancer patients. These findings elucidate the mechanism by which USP33 augments ovarian Cancer progression through the stabilization of CBX2, underscoring the USP33-CBX2 axis as a promising therapeutic target in ovarian Cancer management.

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