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Abstract
An interaction between ribosomal protein S3 (rpS3) and nuclear factor kappa B or macrophage migration inhibitory factor in non-small-cell lung cancer is responsible for radioresistance. However, the role of rpS3 in glioblastoma (GBM) has not been investigated to date. Here we found that in irradiated GBM cells, rpS3 translocated into the nucleus and was subsequently ubiquitinated by ring finger protein 138 (RNF138). Ubiquitin-dependent degradation of rpS3 consequently led to radioresistance in GBM cells. To elucidate the apoptotic role of rpS3, we analyzed the interactome of rpS3 in ΔRNF138 GBM cells. Nuclear rpS3 interacted with DNA damage inducible transcript 3 (DDIT3), leading to DDIT3-induced apoptosis in irradiated ΔRNF138 GBM cells. These results were confirmed using in vivo orthotopic xenograft models and GBM patient tissues. This study aims to clarify the role of RNF138 in GBM cells and demonstrate that rpS3 may be a promising substrate of RNF138 for the induction of GBM radioresistance, indicating RNF138 as a potential target for GBM therapy.

Author information

Kim W1, Youn H2, Lee S3, Kim E3, Kim D3, Sub Lee J4, Lee JM5, Youn B1,3.
1
Department of Biological Sciences, Pusan National University, Busan, Republic of Korea.
2
Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.
3
Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.
4
Department of Orthopaedic Surgery, Medical Research Institute, Pusan National University School of Medicine, Busan, Republic of Korea.
5
Department of Naval Architecture and Ocean Engineering, Pusan National University, Busan, Republic of Korea.