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The meteoric rise of regulated intracellular proteolysis

Nature Reviews Molecular Cell Biology volume 1, pages 145–148 (2000)Cite this article

Abstract

It is often the case in biology that research into breaking things down lags behind research into synthesizing them, and this is certainly true for intracellular proteolysis. Now that we recognize that intracellular proteolysis, triggered by attaching multiple copies of a small protein called ubiquitin to target proteins, is fundamental to life, it is hard to believe that 20 years ago this field was little more than a backwater of biochemistry studied by a handful of laboratories. Among the few were Avram Hershko, Aaron Ciechanover and Alexander Varshavsky, who were recently awarded the Albert Lasker award for basic medical research for discovering the importance of protein degradation in cellular physiology. This Timeline traces how they and their collaborators triggered the rapid movement of ubiquitin-mediated proteolysis to centre stage.

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Figure 1: The main proteolytic pathways in eukaryotic cells.
Figure 2: Lewis Carroll's Red Queen.
Figure 3: The fathers of the field of regulated intracellular proteolysis.

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Acknowledgements

I thank Avram Hershko and Aaron Ciechanover (Haifa), Alex Varshavsky (Pasadena), Wolfgang Dubiel (Berlin), Dieter Wolf (Stuttgart), Mark Hochstrasser (Chicago), Peter Zwickl (Martinsreid), Cecile Pickart (Baltimore), Keith Wilkinson (Atlanta), Alan Weissman (Washington), Ron Hay (St Andrews), and Simon Dawson, Michael Landon, Andy Alban and Rob Layfield (Nottingham) for help with this article; Rohan Baker (Canberra) for critically reviewing the manuscript; and the MRC, BBSRC, Wellcome Trust and EU Framework IV for support of some of the quoted work. Numerous pivotal contributions have been omitted due to space constraints; many thanks to the 'unsung heroes'.

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Authors and Affiliations

  1. Laboratory for Intracellular Proteolysis, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH , UK

    R. John Mayer

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  1. R. John Mayer
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FURTHER INFORMATION

Regulatory subunits of the 26S proteasome

Ubiquitin index

The Ciechanover laboratory

The Hershko laboratory

The Varshavsky laboratory

Press Release on the 2000 Albert Lasker Awards

Nature Medicine commentaries

ENCYCLOPEDIA OF LIFE SCIENCES

Ubiquitin pathway

Protease complexes

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John Mayer, R. The meteoric rise of regulated intracellular proteolysis . Nat Rev Mol Cell Biol 1, 145–148 (2000). https://doi.org/10.1038/35040090

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