小鼠白血病病毒 (MLV) P50蛋白通过转录调节功能诱导细胞转化
Charbel Akkawi1, Jerome Feuillard1, Felipe Leon Diaz1
1Team R2D2: Retroviral RNA Dynamics and Delivery, IRIM, UMR9004, CNRS, University of Montpellier, Montpellier, France.
Retrovirology
|September 12, 2023
概括
鼠类白血病病毒的拼接供体 (SD) 相关的逆元件 (SDARE) 产生P50蛋白. 这种P50蛋白扩散到邻近的细胞,并通过转录调节驱动癌症的发展.
科学领域:
- 病毒学 病毒学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 鼠类白血病病毒 (MLV) 是癌症基因发现的关键模型.
- 在MLV拼接供体 (SD') 相关的逆元件 (SDARE) 对于MLV感染性和瘤形成至关重要.
- SDARE在病变发生过程中的作用的确切机制尚不清楚.
研究的目的:
- 为了阐明由MLV的SDARE产生的P50蛋白的功能.
- 调查P50对MLV诱导的癌症有所贡献的机制.
- 探索P50.0.的传播和细胞效应.
主要方法:
- 细胞感染含有SDARE转录的MLV颗粒.
- 细胞转化试验 (CCK8,TUNEL,独立于 anchorage 的生长).
- 路西法酶测定,RT-qPCR和转录基因分析来研究P50的转录活性.
主要成果:
- SDARE可以通过P50蛋白通过邻近的细胞传播.
- P50蛋白诱导细胞转化并促进瘤发生.
- P50的整合酶域对MLV促进体进行转调,放松了数百种与癌症相关的细胞RNAs的调节.
结论:
- 由SDARE调解的P50辅助蛋白传播的新机制被提出.
- P50蛋白质的转化特性创造了一个有利于癌症的微环境.
- 通过转录失调,P50作为MLV诱导的致癌的一个关键驱动因素.
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