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Activity-Based Imaging Probes of the Proteasome

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Abstract

Over the years, the proteasome has been extensively investigated due to its crucial roles in many important signaling pathways and its implications in diseases. Two proteasome inhibitors—bortezomib and carfilzomib—have received FDA approval for the treatment of multiple myeloma, thereby validating the proteasome as a chemotherapeutic target. As a result, further research efforts have been focused on dissecting the complex biology of the proteasome to gain the insight required for developing next-generation proteasome inhibitors. It is clear that chemical probes have made significant contributions to these efforts, mostly by functioning as inhibitors that selectively block the catalytic activity of proteasomes. Analogues of these inhibitors are now providing additional tools for visualization of catalytically active proteasome subunits, several of which allow real-time monitoring of proteasome activity in living cells as well as in in vivo settings. These imaging probes will provide powerful tools for assessing the efficacy of proteasome inhibitors in clinical settings. In this review, we will focus on the recent efforts towards developing imaging probes of proteasomes, including the latest developments in immunoproteasome-selective imaging probes.

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Acknowledgments

We gratefully acknowledge the National Institutes of Health for their financial support (R01 CA128903).

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All authors declare that they have no conflict of interest.

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  1. Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, 40536-0596, USA

    Kimberly Cornish Carmony & Kyung Bo Kim

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  1. Kimberly Cornish Carmony
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Correspondence to Kyung Bo Kim.

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Carmony, K.C., Kim, K.B. Activity-Based Imaging Probes of the Proteasome. Cell Biochem Biophys 67, 91–101 (2013). https://doi.org/10.1007/s12013-013-9626-4

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