Year: 2025
Type: article
Abstract: Radiotherapy is a therapeutic mainstay for nasopharyngeal carcinoma (NPC), exploiting ionizing radiation to induce lethal DNA damage in cancer cells. Most patients respond well, yet approximately 20% relapse after curative treatment [ 1 ]. Accumulating evidence implicates activation of DNA damage repair (DDR) pathways in radioresistance [ 2 , 3 ], however, the underlying mechanisms remain elusive. In the present issue of Cell Death & Differentiation, the manuscript entitled “USP18 promotes nasopharyngeal carcinoma radioresistance via TRIM29 oligomerization and ubiquitination” by Lin and collaborators uncovers that the Ubiquitin specific peptidase 18 (USP18) plays a key role in NPC radioresistance [ 4 ]. Mechanistically, USP18 acts as a scaffold protein, independently of its deubiquitinase (DUB) activity, promoting DDR that shields NPC cells from radiation-induced death (Fig. 1 ). Fig. 1: Role of the USP18–TRIM21–TRIM29 axis in nasopharyngeal carcinoma radioresistance. Following radiotherapy, USP18 is upregulated and scaffolds the formation of a protein complex in which TRIM21 ubiquitinates TRIM29. This modification promotes TRIM29 oligomerization and nuclear translocation, thereby enhancing the DDR, ultimately contributing to radioresistance and tumor progression. Genetic ablation of USP18 impairs TRIM21-TRIM29 interaction, and thus TRIM29-dependent DDR, sensitizing cancer cells to radio-induced DNA damage and consequent apoptosis. The image was made in BioRender.com. Full size image
Source: Cell Death and Differentiation
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
Awards: G4711398819, G8853665404
OpenAlex ID: W4416122771