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Human adenovirus oncolytic properties and the inhibitory role of E4 orf4 and E4 orf6/7 on endogenously activated NF-κ B
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| Title: | Human adenovirus oncolytic properties and the inhibitory role of E4 orf4 and E4 orf6/7 on endogenously activated NF-κ B |
| Other Titles: | ヒトアデノウイルス E4 orf4 および E4 orf6/7 のNF-κ B 抑制作用と腫瘍溶解性 |
| Authors: | 王, 安然 Browse this author |
| Keywords: | Adenovirus | | E4 orf4 | | E4 orf6/7 | | NF-κB | | TLR2 |
| Issue Date: | 25-Mar-2024 |
| Publisher: | Hokkaido University |
| Abstract: | Human adenovirus is a promising tool for cancer therapy as an oncolytic virus. To predict which region of the oncolytic adenovirus E4 gene could be deleted, we investigated the relationship between the E4 proteins and NF-κB. Here, we report that TLR2-dependent NF-κB activation in Ad5-infected cells was significantly inhibited 24 h post-infection. Among the six E4 proteins, E4 orf4 and E4 orf6/7 exhibited notable suppressive effects on NF-κB activation. However, only E4 orf4 was co-immunoprecipitated with the RelA protein, also known as p65. It appears likely that E4 orf6/7 represses NF-κB activation via E2F-dependent pathways. Our results suggest that both E4 orf4 and E4 orf6/7 are novel inhibitors of NF-κB activation. The inhibition of endogenous NF-κB activation by E4 proteins during the late phase of infection also appears to elucidate the previously reported suppression of E1A expression in the late phase of infection. These redundant suppressive effects of E4 orf4 and E4 orf6/7 on NF-κB suggest that these proteins may play a major role in the anticancer properties of oncolytic adenovirus. |
| Conffering University: | 北海道大学 |
| Degree Report Number: | 甲第15931号 |
| Degree Level: | 博士 |
| Degree Discipline: | 歯学 |
| Examination Committee Members: | (主査) 教授 長谷部 晃, 教授 飯村 忠浩, 教授 樋田 京子, 教授 横山 敦郎, 准教授 安田 元昭 |
| Degree Affiliation: | 歯学院(口腔医学専攻) |
| Type: | theses (doctoral) |
| URI: | http://hdl.handle.net/2115/92134 |
| Appears in Collections: | 課程博士 (Doctorate by way of Advanced Course) > 歯学院(Graduate School of Dental Medicine)
学位論文 (Theses) > 博士 （歯学）
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