抑制性癌症不间断扩展突变增加C端水性,并破坏进化保存的氨基酸模式
Avantika Ghosh1,2, Marisa Riester1, Jagriti Pal1
1Division of Cancer Research, Department of Thoracic Surgery, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.
不间断扩展突变可以降低癌症中的蛋白质水平. 这些突变影响瘤抑制基因,它们的有效性与增加的C-终端水性有关.
科学领域:
- 基因组学就是基因组学.
- 蛋白质组学是指蛋白质组学.
- 癌症生物学 癌症生物学
背景情况:
- 非停止延伸突变 (停止损失) 通过改变停止编码子来创建具有延伸C终端的蛋白质.
- 虽然在癌症中已知SMAD4不间断突变,但其他突变的影响在很大程度上仍未被描述.
研究的目的:
- 系统地评估2335个体质不间断突变衍生的C终端延伸在癌症中对蛋白质表达的影响.
- 确定有效的C端延伸的特征及其与进化模式的关系.
主要方法:
- 使用泛癌NonStopDB数据集进行分析.
- 进行高通量选以评估蛋白质丰度变化.
- 分析了C端氨基酸组成和水性.
- 对比癌症衍生的扩展与跨物种的进化保存的C-终端模式.
主要成果:
- 56.1%的C端延伸显著降低了蛋白质丰度.
- 在包括PTEN,APC,B2M,CASP8,CDKN1B和MLH1.1在内的瘤抑制基因中发现了有效的扩展.
- 较高的疏水性与有效的蛋白质不稳定性相关.
- 癌症衍生的扩展破坏了保存的进化C端氨基酸分布模式.
结论:
- 身体的不间断突变经常导致癌症中的蛋白质不稳定.
- C端水性是这些扩展所导致的蛋白质不稳定的一个关键决定因素.
- 癌症突变对进化保存的C端特征的破坏具有功能后果.
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