Abstract
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.
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Acknowledgements
Research in the author's laboratory is supported by grants from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF), the Israel Science Foundation (ISF), the Israeli Centers for Research Excellence (I-CORE) Program of the Israeli Planning and Budgeting Committee and the Israel Science Foundation (ISF) (Grant1775/12), the EU Treat PolyQ Network, and the Deutsch-Israelische Projektkooperation (DIP). The author is an Israel Cancer Research Fund (ICRF) USA professor.
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Ciechanover, A. The unravelling of the ubiquitin system. Nat Rev Mol Cell Biol 16, 322–324 (2015). https://doi.org/10.1038/nrm3982
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DOI: https://doi.org/10.1038/nrm3982
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