乌比基特异性蛋白酶7稳定HPV16E7以促进HPV介导的癌变发生
Chichao Xia1, Chuanyun Xiao1, Ho Yin Luk1
1Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR.
Cellular and molecular life sciences : CMLS
|September 8, 2023
概括
人类乳头瘤病毒 (HPV) E7上蛋白稳定性由宿主de-ubiquitinaseUSP7.7保持. 用HBX 19818抑制USP7降低了E7水平,并阻止了HPV驱动的癌症进展.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 人类乳头瘤病毒 (HPV) 蛋白,如E7,对于病毒复制和癌症发展至关重要.
- 通过操纵宿主去无化通路,HPV保持了病毒蛋白的稳定性.
研究的目的:
- 为了研究HPV E7coprotein和宿主去-ubiquitinating酶之间的相互作用.
- 为了确定在HPV E7蛋白稳定性中全素特异蛋白酶7 (USP7) 的作用.
- 评估USP7抑制在HPV相关癌症中的治疗潜力.
主要方法:
- 同免疫沉检测HPV16E7-USP7复合体的形成.
- 西方涂抹测试以评估蛋白质水平和半衰期.
- 基于细胞的测试以测量扩散,入侵,迁移和转变.
- 用USP7抑制剂HBX 19818.8进行治疗.
主要成果:
- HPV16E7通过E7-CR3域与USP7相互作用,形成一个核复合体.
- USP7通过抑制全方位化和蛋白质体降解来稳定HPV16E7,延长其半衰期.
- 用HBX 19818抑制USP7降低了HPV16E7水平,并阻止了HPV介导的致癌.
结论:
- USP7对于稳定HPV E7上蛋白质至关重要.
- 用HBX 19818针对USP7显示出治疗HPV相关癌症的巨大潜力.
- 抑制USP7提供了针对HPV驱动的恶性瘤的新治疗策略.
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