胆固醇中间体与交配费洛蒙前体以及ras蛋白的酶性合
W R Schafer1, C E Trueblood, C C Yang
1Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Science (New York, N.Y.)
|September 7, 1990
概括
酵母中的DPR1-RAM1基因产物对于蛋白质前转移酶活性至关重要,这是翻译后修改的关键步骤. 这一发现对了解前化蛋白和潜在的抗癌药物标有影响.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 细胞生物学 细胞生物学
背景情况:
- 像Ras,核层和G蛋白质这样的蛋白质的翻译后修饰涉及复杂的炭基终端处理.
- 这种加工包括前化,蛋白质分解裂变和碳氧甲基化,这对蛋白质功能至关重要.
- 酵母菌Saccharomyces cerevisiae在这些修饰中使用了DPR1-RAM1基因产物.
研究的目的:
- 研究DPR1-RAM1基因产物在酵母蛋白转化后加工中的作用.
- 为了确定与DPR1-RAM1.1.相关的特定酶活性.
- 探索这些发现对人类蛋白质加工和癌症治疗的影响.
主要方法:
- 在体外测试中使用模仿酵母甲配合激素前体的基质.
- 引入了DPR1-RAM1基因的突变,以观察对处理的影响.
- 评估了酵母蛋白prenyltransferase在酵母和人类基质上的前化活性.
主要成果:
- 在DPR1-RAM1中发生的突变导致了蛋白质加工的前化阶段的缺陷.
- DPR1-RAM1被确定为一种蛋白质前转移酶的必不可少和限制速率的组成部分.
- 确定了三个加工步骤的固定顺序:先化,蛋白质分解和碳基甲基化.
- 证明酵母蛋白前转移酶可以先化人类的H-ras p21前体.
结论:
- DPR1-RAM1基因产物对于酵母中蛋白质前化至关重要.
- 鉴定出的蛋白质前转移酶是翻译后修改途径中的关键酶.
- DPR1-RAM1的人类同类代表了抗癌化疗的潜在治疗标.
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