Pub Date : 2025-11-11DOI: 10.1038/s41418-025-01616-2
Francesco Napoletano, Rebecca Bertolio, Giannino Del Sal
{"title":"Ubiquitin choreography in nasopharyngeal carcinoma: USP18 scaffolds radioresistance","authors":"Francesco Napoletano, Rebecca Bertolio, Giannino Del Sal","doi":"10.1038/s41418-025-01616-2","DOIUrl":"https://doi.org/10.1038/s41418-025-01616-2","url":null,"abstract":"","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"22 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"USP18 promotes nasopharyngeal carcinoma radioresistance via TRIM29 oligomerization and ubiquitination","authors":"Jia-Yi Lin, Jun-Xiang Chen, Zi-Chen Qiu, Wei-Wei Zhang, Qing-Jie Li, Jun-Yan Li, Xu Jiang, Yu-Han Hu, Shi-Wei He, Shan Zhang, Ying-Qin Li, Na Liu, Jun Ma, Yin Zhao, Rui Guo","doi":"10.1038/s41418-025-01615-3","DOIUrl":"https://doi.org/10.1038/s41418-025-01615-3","url":null,"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.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"163 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1038/s41418-025-01614-4
Yan Gao, Zhuo Zhao, Xuepin Chen, Nuo Li, Ying Li, Jun Guan, Hongyan Dai
{"title":"RNF220 mediates K63-linked polyubiquitination of STAT3 and aggravates pathological cardiac hypertrophy","authors":"Yan Gao, Zhuo Zhao, Xuepin Chen, Nuo Li, Ying Li, Jun Guan, Hongyan Dai","doi":"10.1038/s41418-025-01614-4","DOIUrl":"https://doi.org/10.1038/s41418-025-01614-4","url":null,"abstract":"","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"29 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1038/s41418-025-01612-6
Diyun Xu, Jibo Han, Bozhi Ye, Liming Lin, Jiaji Chen, Yanhong Jin, Ying Zhao, Yi Wang, Peiren Shan, Guang Liang
{"title":"USP13 ameliorates diabetic cardiomyopathy via deubiquitinating NLRP3 and inhibiting pyroptosis in cardiomyocytes","authors":"Diyun Xu, Jibo Han, Bozhi Ye, Liming Lin, Jiaji Chen, Yanhong Jin, Ying Zhao, Yi Wang, Peiren Shan, Guang Liang","doi":"10.1038/s41418-025-01612-6","DOIUrl":"https://doi.org/10.1038/s41418-025-01612-6","url":null,"abstract":"","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"82 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1038/s41418-025-01601-9
S. L. Petersen, T. T. Chen, D. A. Lawrence, S. A. Marsters, F. Gonzalvez, A. Ashkenazi
{"title":"Correction: TRAF2 is a biologically important necroptosis suppressor","authors":"S. L. Petersen, T. T. Chen, D. A. Lawrence, S. A. Marsters, F. Gonzalvez, A. Ashkenazi","doi":"10.1038/s41418-025-01601-9","DOIUrl":"https://doi.org/10.1038/s41418-025-01601-9","url":null,"abstract":"","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"1 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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