Cancer and Vascular Biology Research Center, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel.
Nat Rev Mol Cell Biol. 2015 May;16(5):322-4. doi: 10.1038/nrm3982.
Today, many scientific discoveries are made using a top-down experimental approach. The ubiquitin system was discovered using a 'classic' bottom-up approach to tackle the question: 'how are cellular proteins selectively degraded?' A simple proteolytic assay, which used a crude cell-extract, was all that was required to address this question; it was followed by fractionation and reconstitution experiments to decipher the role of the components in this multi-step process. This 'biochemistry at its best' approach, which was published in a periodical that today would not be regarded as highly visible, provided magnificent findings.
如今，许多科学发现都是采用自上而下的实验方法取得的。泛素系统是采用经典的自下而上方法发现的，旨在解决“细胞蛋白如何被选择性降解”这一问题。该方法仅需要一个简单的蛋白水解测定实验，使用粗制的细胞提取物，就能解决这个问题；随后通过分级分离和重组实验来阐明这个多步骤过程中各组成部分的作用。这种“处于最佳状态的生物化学”方法发表在当时不会被认为是高度显著的期刊上，但提供了重要的发现。
