TRAIP regulates Histone H2B monoubiquitination in DNA damage response pathways

Han,Ye Gi; Yun,Miyong; Choi,Minji; Lee,Seok‑Geun; Kim,Hongtae

doi:10.3892/or.2019.7092

TRAIP regulates Histone H2B monoubiquitination in DNA damage response pathways

Authors:
- Ye Gi Han
- Miyong Yun
- Minji Choi
- Seok‑Geun Lee
- Hongtae Kim
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Affiliations: Department of Biological Sciences, Sungkyunkwan University, Suwon 440‑746, Republic of Korea, Department of Science in Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea, Center for Genomic Integrity Institute for Basic Science (IBS), Ulsan National Institute of Science and Technology, Ulsan 689‑798, Republic of Korea
Published online on: April 2, 2019 https://doi.org/10.3892/or.2019.7092
Pages: 3305-3312

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Abstract

Histone H2B monoubiquitination has been shown to play critical roles in diverse cellular processes including DNA damage response. Although recent data indicate that H2B monoubiquitination is strongly connected with tumor progression and regulation, the implications of this modification in lung adenocarcinoma are relatively unknown. In the present study, we demonstrated the clinical implication of H2B monoubiquitination and the potential role of tumor necrosis factor receptor‑associated factor‑interacting protein (TRAIP) in regulating its modification in lung adenocarcinoma. Immunohistochemical analysis showed that H2B monoubiquitination was significantly downregulated in 68 human lung adenocarcinoma patient samples compared to their normal adjacent tissues. Depletion of TRAIP by specific siRNA treatment markedly decreased ionizing radiation (IR)‑induced H2B monoubiquitination. In addition, deletion mutants without RING domain or C‑terminus of TRAIP diminished the ability to induce H2B monoubiquitination at lysine 120. Notably, the nuclear expression of TRAIP was positively related with H2B monoubiquitination levels in patients with lung adenocarcinoma. Furthermore, statistical analysis indicated that low levels of both TRAIP and H2B monoubiquitination, not each alone, in patients with lung adenocarcinoma were strongly correlated with poor survival. Taken together, these results suggest that TRAIP is a novel regulator of H2B monoubiquitination in DNA damage response and cancer development in lung adenocarcinoma.

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