Related Experiment Video
Updated: Jan 11, 2026
Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas
Published on: February 28, 2019
USP18 promotes nasopharyngeal carcinoma radioresistance via TRIM29 oligomerization and ubiquitination
Jia-Yi Lin1, Jun-Xiang Chen2, Zi-Chen Qiu1
1Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, 510060, China.
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.
Insights
The study found that ubiquitin specific peptidase 18 (USP18) overexpression in nasopharyngeal carcinoma (NPC) enhances DNA damage repair, reducing radiosensitivity. Targeting the USP18-TRIM21-TRIM29 pathway could improve NPC radiotherapy outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Radiotherapy is a primary treatment for nasopharyngeal carcinoma (NPC), but tumor recurrence remains a challenge.
- DNA damage repair (DDR) pathways, involving ubiquitination, are critical in cancer treatment response.
- Understanding molecular mechanisms of radioresistance in NPC is crucial for improving therapeutic efficacy.
Purpose of the Study:
- To investigate the role of ubiquitin specific peptidase 18 (USP18) in NPC radiosensitivity and DNA damage repair.
- To elucidate the interaction between USP18, TRIM29, and TRIM21 in the context of NPC radioresistance.
Main Methods:
- Analysis of USP18 expression in NPC tissues and correlation with radiosensitivity.
- Investigation of USP18-TRIM29 interaction and USP18's effect on TRIM29 ubiquitination.
- Assessment of USP18's role in recruiting TRIM21 and its impact on TRIM29 oligomerization and nuclear translocation.
- Evaluation of the functional consequence of the USP18-TRIM21-TRIM29 axis on DDR and NPC cell radiosensitivity.
Main Results:
- USP18 is overexpressed in radioresistant NPC tissues and inversely correlates with radiosensitivity.
- USP18 interacts with TRIM29, promoting its K27-linked ubiquitination and enhancing DDR.
- USP18 acts as a scaffold for TRIM21, facilitating TRIM29 ubiquitination, oligomerization, and nuclear translocation.
- High USP18 expression is linked to poorer patient prognosis, indicating its clinical significance.
Conclusions:
- USP18 plays a critical role in modulating DDR signaling and radiosensitivity in NPC.
- The USP18-TRIM21-TRIM29 axis is a key regulator of radioresistance in NPC.
- Targeting the USP18-TRIM21-TRIM29 pathway offers a potential strategy to enhance NPC radiotherapy efficacy.
Related Concept Videos
02:23Abnormal Proliferation
01:45Regulation of Nuclear Protein Sorting
02:55The Nucleolus
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...