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USP39-通过ETS2进行非保护主义控制,抑制核定位和活动

Yunsik Choi¹, Yuri Lee¹, Jin Seo Kim¹

¹Department of Life Sciences, Sogang University, Seoul 04107, Republic of Korea.

|October 28, 2023

概括

研究人员发现,USP39是一种二基因酶,与ETS2 (转录因子) 结合,并通过减少其核定位来抑制其活性. 这种相互作用为ETS2相关的癌症提供了潜在的治疗策略.

科学领域:

分子生物学分子生物学
细胞生物学细胞生物学
在瘤学瘤学.

背景情况:

作为ETS家族的一种转录因子,ETS2调节了诸如增殖和亡之类的关键细胞过程.
异常ETS2激活与各种人类癌症有关,使其成为一个重要的治疗点.
了解ETS2调节和相互作用是开发向癌症治疗的关键.

研究的目的:

确定ETS2转录因子的新监管合作伙伴.
调查ETS2及其约束性合作伙伴之间的相互作用的功能后果.
探索在癌症治疗中准ETS2相互作用蛋白质复合物的潜力.

主要方法:

使用结合试验对人类二维基因酶 (DUB) 库的选.
同免疫沉和域映射以确认USP39-ETS2相互作用.
西方涂抹和记者测试以评估ETS2的二氧化和转录活动.
免疫光显微镜来评估ETS2的核定位.

主要成果:

USP39被确定为一种新的ETS2约束DUB.
USP39通过它们的氨基末端区域与ETS2相互作用,独立于特定的域.
USP39对ETS2进行二氧化化,但不会影响其蛋白质稳定性.
USP39显著抑制了ETS2的转录活动,并减少了它的核定位.

结论:

USP39 作为ETS2 功能的负调节器.
USP39和ETS2之间的相互作用影响ETS2的转录活动和亚细胞局部化.
针对USP39-ETS2相互作用可能为ETS2驱动的癌症提供一种新的治疗策略.

关键词:

这是ETS2的第二个版本.USP39 美国39 没有二维基丁酶.转录因子的转录因子

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