title: A bright approach to the immunoproteasome: development of LMP2/β1i-specific imaging probes.
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.
authors: Department of Pharmaceutical Science, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors: Kimberly Cornish
authors: KC
authors: Carmony
authors: Do-Min
authors: DM
authors: Lee
authors: Ying
authors: Y
authors: Wu
authors: Na-Ra
authors: NR
authors: Lee
authors: Marie
authors: M
authors: Wehenkel
authors: Jason
authors: J
authors: Lee
authors: Beilei
authors: B
authors: Lei
authors: Chang-Guo
authors: CG
authors: Zhan
authors: Kyung-Bo
authors: KB
authors: Kim
mesh_terms: D000906:Antibodies / Q000276:immunology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry*; D005452:Fluoresceins / Q000138:chemical synthesis / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; D001896:Boron Compounds; D004151:Dipeptides; D005452:Fluoresceins; D005456:Fluorescent Dyes; C572002:UK101-B660; C572001:UK101-Fluor; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex