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相关实验视频

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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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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
PubMed
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.

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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.