可编程的蛋白质降解剂能够选择性地击败致病性β-catenin亚群in vitro和in vivo
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Reconstitution Of β-catenin Degradation In Xenopus Egg Extract
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Tianzheng Ye1, Azmain Alamgir1, Cara M Robertus2
1Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853 USA.
bioRxiv : the preprint server for biology
|November 28, 2024
概括
设计者无处不在体 (uAbs) 在癌细胞和小鼠肝脏中选择性地降解有害的β-catenin. 这种向蛋白质降解抑制了Wnt信号,抑制了瘤生长,并提供了新的治疗策略.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 异常的Wnt信号通过增加细胞质β-catenin驱动癌症.
- 积累的β-catenin促进基因转录,导致细胞增殖和恶性瘤.
研究的目的:
- 开发设计型无处不在体 (uAbs),用于选择性降解致病性β-catenin.
- 利用蛋白质语言模型 (pLM) 进行高效的uAb设计.
主要方法:
- 利用一个pLM驱动的算法 (SaLT&PepPr) 来设计β-catenin向.
- 化与Hsp70相互作用蛋白 (CHIP) E3酶的C端结合,以创建uAbs.
- 在结直肠癌细胞中表达uAbs,并在小鼠中通过脂质纳米颗粒 (LNP) 传递.
主要成果:
- 确定了uAb设计,可以显著降低细胞和核β-catenin,同时节省与膜相关的β-catenin.
- 已证明抑制Wnt/β-catenin信号传递,损害瘤细胞的存活和增殖.
- 在LNP-mRNA输送后,在小鼠肝脏中展示了细胞质β-catenin的选择性降低.
结论:
- uAbs可以在体外和体内选择性地消除异常蛋白质.
- 体引导的uabs代表了一种针对致病蛋白质的新方法.
- 这项技术为类可编程生物调节器开辟了道路.
关键词:
E3 无处不在的合酶在Wnt/β-catenin信号传输中.生物PROTACs的使用方法生物降解剂 生物降解剂机器学习是机器学习.非抗体支架的非抗体支架后翻译修改后的修改蛋白质语言模型的模型靠近诱导的蛋白质组编辑有针对性的蛋白质降解降解.无处不在的化更多相关视频
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