USP18 promotes nasopharyngeal carcinoma radioresistance via TRIM29 oligomerization and ubiquitination

Radiotherapy, which induces DNA damage to control the progression of local tumors, is the mainstay therapy for nasopharyngeal carcinoma (NPC). However, almost a fifth of patients undergo recurrence. Evidence suggests that ubiquitination is crucial in DNA damage repair (DDR) signaling. In this study, we reveal that the ubiquitin specific peptidase 18 (USP18) is significantly overexpressed in resistant NPC tissues and correlates inversely with NPC cell radiosensitivity. Our findings indicate that USP18 interacts with tripartite motif containing 29 (TRIM29), facilitating its K27-linked ubiquitination independent of USP18's catalytic activity. USP18 functions as a scaffold, recruiting the E3 ubiquitin ligase tripartite motif containing 21 (TRIM21), which directly ubiquitinates TRIM29 at Lys561. This process promotes TRIM29 oligomerization and nuclear translocation, which enhances DDR in NPC cells after radiotherapy. Clinically, high USP18 levels are associated with worse patient prognosis. Our findings underscore the critical role of USP18 in modulating DDR signaling and radiosensitivity in NPC, suggesting that targeting the USP18-TRIM21-TRIM29 axis may represent a novel strategy to enhance the efficacy of radiotherapy for patients with NPC.

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Publication Details

Journal
Cell Death and Differentiation
Published
2025-11-11
DOI
https://doi.org/10.1038/s41418-025-01615-3
Citations
1
Primary Topic
interferon and immune responses
Type
article
Field-Weighted Citation Impact
0.80

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article

USP18 promotes nasopharyngeal carcinoma radioresistance via TRIM29 oligomerization and ubiquitination

Ying‐Qin Li, Weizheng Zhang, Zichen Qiu, J. Chen et al.
1 citations
Cell Death and Differentiation
interferon and immune responses
0.80
article

USP18 promotes nasopharyngeal carcinoma radioresistance via TRIM29 oligomerization and ubiquitination

Ying‐Qin Li, Weizheng Zhang, Zichen Qiu, J. Chen, Qingjie Li, Yin Zhao, Shan Zhang, Na Liu, Jun Ma, Junyan Li, Jiayi Lin, Rui Guo, Shiwei He, Yuhan Hu, Xu Jiang
article en
1 citations

Abstract

Radiotherapy, which induces DNA damage to control the progression of local tumors, is the mainstay therapy for nasopharyngeal carcinoma (NPC). However, almost a fifth of patients undergo recurrence. Evidence suggests that ubiquitination is crucial in DNA damage repair (DDR) signaling. In this study, we reveal that the ubiquitin specific peptidase 18 (USP18) is significantly overexpressed in resistant NPC tissues and correlates inversely with NPC cell radiosensitivity. Our findings indicate that USP18 interacts with tripartite motif containing 29 (TRIM29), facilitating its K27-linked ubiquitination independent of USP18's catalytic activity. USP18 functions as a scaffold, recruiting the E3 ubiquitin ligase tripartite motif containing 21 (TRIM21), which directly ubiquitinates TRIM29 at Lys561. This process promotes TRIM29 oligomerization and nuclear translocation, which enhances DDR in NPC cells after radiotherapy. Clinically, high USP18 levels are associated with worse patient prognosis. Our findings underscore the critical role of USP18 in modulating DDR signaling and radiosensitivity in NPC, suggesting that targeting the USP18-TRIM21-TRIM29 axis may represent a novel strategy to enhance the efficacy of radiotherapy for patients with NPC.

Cell Death and Differentiation
Sun Yat-sen University (CN), Key Laboratory of Guangdong Province (CN), Sun Yat-sen University Cancer Center (CN), State Key Laboratory of Oncology in South China
National Natural Science Foundation of China, Sun Yat-sen University, Guangzhou Municipal Science and Technology Project, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, Sun Yat-sen University Cancer Center
Openalex Percentile: Top 22%
interferon and immune responses
0.80
DOIOpen Access PDFOpenAlex
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