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酸化依赖的二维基基因酶OTUD3调节YY1的稳定性,并促进结直肠癌的进展
Liang Wu1, Zili Zhou2, Yang Yu3,4
1Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Heifei, 230001, China.
Cell death & disease
|February 13, 2024
概括
研究人员将OTUD3确定为阴阳1 (YY1) 的二基因酶. OTUD3稳定YY1,促进结肠直肠癌 (CRC) 的扩散,这表明CRC的治疗点.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 阴阳1 (YY1) 是一种关键的转录因子,与各种癌症有关.
- YY1的稳定性是由无素-蛋白酶体系统调节的,但未完全理解二基酶 (DUBs) 的作用.
研究的目的:
- 为了识别与YY1.1相互作用的DUBs.
- 研究OTUD3在调节YY1稳定性的作用及其对结直肠癌 (CRC) 进展的影响.
主要方法:
- 查与YY1.1相互作用的泛素特异蛋白酶.
- 调查OTUD3过度表达,淘汰和淘汰对YY1水平和CRC细胞增殖的影响.
- 分析PLK1-介导酸化在OTUD3-YY1相互作用中的作用.
- 在CRC组织中将OTUD3和YY1表达与患者预后相关联.
主要成果:
- OTUD3被确定为YY1.1的DUB.
- OTUD3的过度表达增加了YY1蛋白水平,并促进了CRC的扩散.
- 淘汰OTUD3或淘汰降低了YY1水平并抑制了CRC增殖.
- 通过PLK1介导的OTUD3酸化增强了OTUD3的结合和YY1.1的脱化.
- 在CRC组织中增加OTUD3和YY1表达与预后不佳相关.
结论:
- OTUD3使YY1脱和稳定,促进CRC的扩散.
- OTUD3-YY1通路代表着结直肠癌的潜在治疗标.
- OTUD3在调节YY1稳定性和CRC进展方面发挥着重要作用.
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