USP37作为NRF2蛋白稳定性和HCC中化学抗性的新型调节剂
Shujiao Zhang1,2, Feihu Ding2, Fuxin Jia2
1Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Discover oncology
|March 13, 2025
概括
乌比基特异蛋白酶37 (USP37) 在肝癌中使核因子 (红色素衍生的2) - - 类似2 (NRF2) 脱并稳定. 抑制USP37会增加NRF2的降解,增强肝细胞癌 (HCC) 中的抗化学性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 化学抵抗在癌症治疗中构成了重大挑战,导致患者的治疗结果不佳.
- 核因子 (红色素衍生2) 类似2 (NRF2) 是一种转录因子,参与细胞抗氧化反应,增殖和化学抵抗,使其成为肝细胞癌 (HCC) 的潜在治疗标.
- 已知通过KEAP1-CUL3 E3结合酶复合体的ubiquitination对NRF2的调节,但duibiquitinases (DUBs) 在肝癌中的作用在很大程度上仍未被描述.
研究的目的:
- 在肝细胞癌 (HCC) 中识别特定的调节核因子 (红色素衍生的2) - - 类似2 (NRF2) 的二维基基因酶 (DUB).
- 阐明这种DUB影响NRF2稳定性的机制及其对化学抵抗的影响.
主要方法:
- 研究了乌比基特异蛋白酶37 (USP37) 和NRF2.2.之间的相互作用.
- 通过酶测试,评估USP37对NRF2二氧化和蛋白质稳定性的影响.
- 在人类HCC患者样本中分析了USP37和NRF2蛋白水平.
- 进行了USP37的淘汰实验,以评估NRF2降解和化学敏感性的变化.
主要成果:
- 乌比基特异蛋白酶37 (USP37) 被确定为NRF2蛋白稳定性的新型调节剂.
- USP37直接与NRF2相互作用,并以酶活性依赖的方式促进其二维基因化.
- 增加的USP37表达与人类HCC样本中增加的NRF2蛋白水平相关.
- 敲除USP37会导致增强NRF2降解,并增加HC细胞对化疗的敏感性.
结论:
- USP37-NRF2轴在调节肝细胞癌 (HCC) 中的化学抵抗方面发挥着至关重要的作用.
- USP37作为NRF2的二维基因酶,稳定其蛋白质水平,并促进化学抵抗.
- 准USP37-NRF2相互作用是一个潜在的治疗策略,以克服HC的化学抵抗.
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