A Bright Approach to the Immunoproteasome: Development of LMP2/β1i-specific Imaging Probes

Overview

Journal Bioorg Med Chem

Specialties Biochemistry
Chemistry

Date 2011 Jul 12

PMID 21741845

Citations 8

Authors

Kimberly Cornish Carmony

Do-Min Lee

Ying Wu

Na-Ra Lee

Marie Wehenkel

Jason Lee

Beilei Lei

Chang-Guo Zhan

Kyung-Bo Kim

Affiliations

Soon will be listed here.

Abstract

While the constitutive, 26S proteasome plays an important role in regulating many important cellular processes, a variant form known as the immunoproteasome is thought to primarily function in adaptive immune responses. However, recent studies indicate an association of immunoproteasomes with many physiological disorders such as cancer, neurodegenerative, and inflammatory diseases. Despite this, the detailed functions of the immunoproteasome remain poorly understood. Immunoproteasome-specific probes are essential to gain insight into immunoproteasome function. Here, we describe for the first time the development of cell-permeable activity-based fluorescent probes, UK101-Fluor and UK101-B660, which selectively target the catalytically active LMP2/β1i subunit of the immunoproteasome. These probes facilitate rapid detection of the cellular localization of catalytically active immunoproteasomes in living cells, providing a valuable tool to analyze immunoproteasome functions. Additionally, as LMP2/β1i may serve as a potential tumor biomarker, an LMP2/β1i-targeting fluorescent imaging probe may be applicable to a rapid readout assay to determine tumor LMP2/β1i levels.

Citing Articles

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Elucidating the catalytic subunit composition of distinct proteasome subtypes: a crosslinking approach employing bifunctional activity-based probes.

Cornish Carmony K, Sharma L, Lee D, Park J, Lee W, Kim K Chembiochem. 2014; 16(2):284-92.

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A FRET-based approach for identification of proteasome catalytic subunit composition.

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