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
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掲載情報:
Scientific Reports
ISSN:
2045-2322  CiNii Research  Webcat Plus  JAIRO
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
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URL:
http://hdl.handle.net/20.500.12000/47286
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