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The human papillomavirus E6 protein targets apoptosis-inducing factor (AIF) for degradation
- 資料種別:
- 論文(リポジトリ)
- 責任表示:
- Shimada, Masaru ; Yamashita, Akio ; Saito, Manami ; Ichino, Motohide ; Kinjo, Takao ; Mizuki, Nobuhisa ; Klinman, Dennis M. ; Okuda, Kenji
- 言語:
- 英語
- 出版情報:
- Springer Nature, 2020-08-26
- 著者名:
Shimada, Masaru Yamashita, Akio Saito, Manami Ichino, Motohide Kinjo, Takao Mizuki, Nobuhisa Klinman, Dennis M. Okuda, Kenji - 掲載情報:
- Scientific Reports
- ISSN:
- 2045-2322
- 巻:
- 10
- バージョン:
- VoR
- 概要:
- Oncoprotein E6 of high-risk human papillomavirus (HPV) plays a critical role in inducing cell immortalization and malignancy. E6 downregulates caspase-dependent pathway through the degradation of p53. However, the effect of HPV E6 on other
…
pathways is still under investigation. In the present study, we found that HPV E6 directly binds to all three forms (precursor, mature, and apoptotic) of apoptosis-inducing factor (AIF) and co-localizes with apoptotic AIF. This binding induced MG132-sensitive reduction of AIF expression in the presence of E6 derived from HPV16 (16E6), a cancer-causing type of HPV. Conversely, E6 derived from a non-cancer-causing type of HPV, HPV6 (6E6), did not reduce the levels of AIF despite its interaction with AIF. Flow cytometric analysis revealed that 16E6, but not 6E6, suppressed apoptotic AIF-induced chromatin degradation (an indicator of caspase-independent apoptosis) and staurosporine (STS, a protein kinase inhibitor)-induced apoptosis. AIF knockdown reduced STS-induced apoptosis in both of 16E6-expressing and 6E6-expressing cells; however, the reduction in 16E6-expressing cells was lower than that in 6E6-expressing cells. These findings indicate that 16E6, but not 6E6, blocks AIF-mediated apoptosis, and that AIF may represent a novel therapeutic target for HPV-induced cervical cancer.
論文 続きを見る - URL:
- http://hdl.handle.net/20.500.12000/47286