Transglutaminase 2 nuclear localization enhances glioblastoma radiation resistance

Radiotherapy remains the cornerstone of treatment for glioblastoma (GBM). However, the frequent occurrence of radiation resistance presents a significant therapeutic challenge. A comprehensive understanding of the mechanisms underlying this resistance is essential for improving GBM treatment strategies. In the present study, live-dead cell staining and immunofluorescence staining were employed, and irradiation-resistant cell lines were established. It was observed that transglutaminase 2 (TGM2) plays a pivotal role in enhancing radiation resistance in GBM, facilitating cell proliferation, and promoting DNA damage repair following irradiation. Moreover, immunofluorescence and nucleoplasmic protein extraction assays revealed that TGM2 in GBM rapidly translocates into the nucleus upon irradiation. Through co-immunoprecipitation assays, TGM2 was identified as binding to an increased amount of p53 proteins, thereby promoting p53 degradation post-irradiation. Notably, inhibition of this interaction resulted in a reduction of radiation resistance in GBM. In summary, this study underscores the significance of TGM2 nuclear translocation in radiation resistance and suggests that disrupting TGM2 binding to p53 may offer novel therapeutic insights for overcoming radiation resistance in GBM.