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Active-site directed probes to report enzymatic action in the ubiquitin proteasome system

Nature Reviews Cancer volume 7, pages 613–620 (2007)Cite this article

Abstract

Irreversible covalent inhibitors equipped with reporter groups, also termed activity-based probes, allow the study of target enzymes based on catalytic activity instead of expression level, which does not necessarily indicate protein function and subsequent cellular consequences. Activity-based probes offer advantages over traditional techniques: they can be applied to the cell or tissue of choice and molecular imaging and pharmacology applications are possible. Here the design and use of probes directed at enzymatic activities in the ubiquitin proteasome system are discussed. This system holds promise for the development of new, targeted anticancer therapies and the probes discussed here might aid in fulfilling this promise.

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Figure 1: The ubiquitin proteasome system.
Figure 2: Development of chemical activity-based probes that directly report enzymatic activity.
Figure 3: Probes to study proteasome and DUB activity.
Figure 4: Applications of mechanism-based active-site directed probes for detection of proteasome and DUB activity.

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Acknowledgements

Research in the Ovaa laboratory is supported by grants from the Netherlands Foundation for Scientific Research (700.55.018 and 700.55.422) and The Netherlands Cancer Society (NKI 2005-3368).

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  1. Huib Ovaa is at the Division of Cellular Biochemistry, Netherlands Cancer Institute (NKI), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. h.ovaa@nki.nl,

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Overview of active site–directed proteasome probes (PDF 181 kb)

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Ovaa, H. Active-site directed probes to report enzymatic action in the ubiquitin proteasome system. Nat Rev Cancer 7, 613–620 (2007). https://doi.org/10.1038/nrc2128

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