相关实验视频
Updated: Jul 25, 2025

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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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乙化向嵌合体使瘤抑制剂p53的乙化成为可能
Md Kabir1, Ning Sun1, Xiaoping Hu1
1Mount Sinai Center for Therapeutics Discovery, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Journal of the American Chemical Society
|June 27, 2023
概括
通过乙化激活p53瘤抑制蛋白. 这种方法成功地准了p53Y220C突变的癌细胞,提供了新的治疗途径.
科学领域:
- 生物化学
- 分子生物学
- 癌症学
背景情况:
- 化学诱导的近距离技术,
- 针对瘤抑制蛋白进行药理激活仍然是癌症治疗中的一个挑战.
研究的目的:
- 引入针对蛋白质乙化的新型AceTAC策略.
- 开发和描述p53瘤抑制蛋白的特定AceTAC.
主要方法:
- 第一个p53Y220C AceTAC的发现和描述,MS78.
- 用MS78来招募p300/CBP基因组乙转移酶进行p53Y220C乙化.
- 评估MS78对癌细胞增殖,克隆性和基因表达 (RNA-seq) 的影响.
主要成果:
- 在K382中MS78以剂量,时间和p300依赖的方式有效乙化p53Y220C.
- 在p53Y220C突变癌细胞中抑制了MS78的增殖和克隆性,对野生型p53细胞的毒性最小.
- 通过MS78的乙化导致TRAIL亡基因的上调和DNA损伤反应途径的下调.
结论:
- 通过乙化,AceTAC策略为向蛋白质 (包括瘤抑制剂) 提供了可通用的平台.
- 在p53Y220C突变的癌症中,MS78具有潜在的治疗作用.
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