实时搜索辅助的多重复合量化蛋白质学揭示了非规范性的短开放阅读框架的系统范围的翻译调节
Hiroko Kozuka-Hata1, Tomoko Hiroki1, Naoaki Miyamura1
1Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Biomolecules
|June 28, 2023
概括
这项研究透露了新的癌症药物标,通过分析对酸酸酸 (SAHA) 的反应中蛋白质组范围内的变化. 该研究确定了非正规的短开放读取 (ORF) 的新和它们在癌细胞中的调节.
科学领域:
- 蛋白质组学是指蛋白质组学.
- 癌症生物学 癌症生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 异常的基因组脱乙酶 (HDAC) 表达与癌症进展有关,包括血管新生,转移和化疗耐药性.
- 苏贝罗伊兰尼利德酸 (SAHA) 是一种已知的HDAC泛抑制剂,用于表观遗传癌症治疗.
- 了解药物诱导的蛋白质组动态对于开发向癌症治疗至关重要.
研究的目的:
- 建立一个实时搜索 (RTS) 辅助的质谱平台,用于从正规和非正规的开放阅读框架 (ORF) 量化翻译产品.
- 为了研究在人类癌细胞中对酸 (SAHA) 治疗的蛋白质组范围的调节效应.
- 为了识别新型和评估转化调节对药物干扰的反应.
主要方法:
- 开发一个实时搜索 (RTS) 辅助的质谱平台,用于全面的蛋白质组分析.
- 用酸 (SAHA) 处理的人类HeLa细胞的定量蛋白质组分析.
- 利用核糖体分析数据来识别非编码和其他RNA转录中的短ORF中的.
主要成果:
- 在假定非编码序列,lncRNA和NMD转录中,通过短ORF编码的约5000种新的识别.
- 在SAHA治疗后,证明了非正规短ORF子集的剂量依赖的选择性翻译调节.
- 观察到关键细胞周期和与增殖相关的分子的调节,包括UBE2C,CENPF和PRC1.
结论:
- 这项研究提供了第一个全系统范围的药物扰乱的转化调制,影响人类癌细胞中的正规和非正规蛋白质组的前景.
- 开发的RTS辅助平台可以进行深入的蛋白质基因分析,发现以前没有注释的翻译产品.
- 这些发现凸显了在癌症治疗中准非正典ORF及其调节途径的潜力.
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