A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo

Martijn Verdoes; Bogdan I Florea; Victoria Menendez-Benito; Christa J Maynard; Martin D Witte; Wouter A van der Linden; Adrianus M C H van den Nieuwendijk; Tanja Hofmann; Celia R Berkers; Fijs W B van Leeuwen; Tom A Groothuis; Michiel A Leeuwenburgh; Huib Ovaa; Jacques J Neefjes; Dmitri V Filippov; Gijs A van der Marel; Nico P Dantuma; Herman S Overkleeft

doi:10.1016/j.chembiol.2006.09.013

A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo

Martijn Verdoes, Bogdan I Florea, Victoria Menendez-Benito, Christa J Maynard, Martin D Witte, Wouter A van der Linden, Adrianus M C H van den Nieuwendijk, Tanja Hofmann, Celia R Berkers, Fijs W B van Leeuwen, Tom A Groothuis, Michiel A Leeuwenburgh, Huib Ovaa, Jacques J Neefjes, Dmitri V Filippov, Gijs A van der Marel, Nico P Dantuma, Herman S Overkleeft

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Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The proteasome is an essential evolutionary conserved protease involved in many regulatory systems. Here, we describe the synthesis and characterization of the activity-based, fluorescent, and cell-permeable inhibitor Bodipy TMR-Ahx(3)L(3)VS (MV151), which specifically targets all active subunits of the proteasome and immunoproteasome in living cells, allowing for rapid and sensitive in-gel detection. The inhibition profile of a panel of commonly used proteasome inhibitors could be readily determined by MV151 labeling. Administration of MV151 to mice allowed for in vivo labeling of proteasomes, which correlated with inhibition of proteasomal degradation in the affected tissues. This probe can be used for many applications ranging from clinical profiling of proteasome activity, to biochemical analysis of subunit specificity of inhibitors, and to cell biological analysis of the proteasome function and dynamics in living cells.

Original language	English
Pages (from-to)	1217-26
Number of pages	10
Journal	Chemistry & Biology
Volume	13
Issue number	11
DOIs	https://doi.org/10.1016/j.chembiol.2006.09.013
Publication status	Published - Nov 2006
Externally published	Yes

Keywords

Animals
Boron Compounds
Cell Line, Tumor
Fluorescent Dyes
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Oligopeptides
Protease Inhibitors
Proteasome Endopeptidase Complex
Proteasome Inhibitors

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10.1016/j.chembiol.2006.09.013

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Verdoes, M., Florea, B. I., Menendez-Benito, V., Maynard, C. J., Witte, M. D., van der Linden, W. A., van den Nieuwendijk, A. M. C. H., Hofmann, T., Berkers, C. R., van Leeuwen, F. W. B., Groothuis, T. A., Leeuwenburgh, M. A., Ovaa, H., Neefjes, J. J., Filippov, D. V., van der Marel, G. A., Dantuma, N. P., & Overkleeft, H. S. (2006). A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo. Chemistry & Biology, 13(11), 1217-26. https://doi.org/10.1016/j.chembiol.2006.09.013

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title = "A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo",

abstract = "The proteasome is an essential evolutionary conserved protease involved in many regulatory systems. Here, we describe the synthesis and characterization of the activity-based, fluorescent, and cell-permeable inhibitor Bodipy TMR-Ahx(3)L(3)VS (MV151), which specifically targets all active subunits of the proteasome and immunoproteasome in living cells, allowing for rapid and sensitive in-gel detection. The inhibition profile of a panel of commonly used proteasome inhibitors could be readily determined by MV151 labeling. Administration of MV151 to mice allowed for in vivo labeling of proteasomes, which correlated with inhibition of proteasomal degradation in the affected tissues. This probe can be used for many applications ranging from clinical profiling of proteasome activity, to biochemical analysis of subunit specificity of inhibitors, and to cell biological analysis of the proteasome function and dynamics in living cells.",

keywords = "Animals, Boron Compounds, Cell Line, Tumor, Fluorescent Dyes, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Oligopeptides, Protease Inhibitors, Proteasome Endopeptidase Complex, Proteasome Inhibitors",

author = "Martijn Verdoes and Florea, {Bogdan I} and Victoria Menendez-Benito and Maynard, {Christa J} and Witte, {Martin D} and {van der Linden}, {Wouter A} and {van den Nieuwendijk}, {Adrianus M C H} and Tanja Hofmann and Berkers, {Celia R} and {van Leeuwen}, {Fijs W B} and Groothuis, {Tom A} and Leeuwenburgh, {Michiel A} and Huib Ovaa and Neefjes, {Jacques J} and Filippov, {Dmitri V} and {van der Marel}, {Gijs A} and Dantuma, {Nico P} and Overkleeft, {Herman S}",

year = "2006",

month = nov,

doi = "10.1016/j.chembiol.2006.09.013",

language = "English",

volume = "13",

pages = "1217--26",

journal = "Chemistry & Biology",

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Verdoes, M, Florea, BI, Menendez-Benito, V, Maynard, CJ, Witte, MD, van der Linden, WA, van den Nieuwendijk, AMCH, Hofmann, T, Berkers, CR, van Leeuwen, FWB, Groothuis, TA, Leeuwenburgh, MA, Ovaa, H, Neefjes, JJ, Filippov, DV, van der Marel, GA, Dantuma, NP & Overkleeft, HS 2006, 'A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo', Chemistry & Biology, vol. 13, no. 11, pp. 1217-26. https://doi.org/10.1016/j.chembiol.2006.09.013

TY - JOUR

T1 - A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo

AU - Verdoes, Martijn

AU - Florea, Bogdan I

AU - Menendez-Benito, Victoria

AU - Maynard, Christa J

AU - Witte, Martin D

AU - van der Linden, Wouter A

AU - van den Nieuwendijk, Adrianus M C H

AU - Hofmann, Tanja

AU - Berkers, Celia R

AU - van Leeuwen, Fijs W B

AU - Groothuis, Tom A

AU - Leeuwenburgh, Michiel A

AU - Ovaa, Huib

AU - Neefjes, Jacques J

AU - Filippov, Dmitri V

AU - van der Marel, Gijs A

AU - Dantuma, Nico P

AU - Overkleeft, Herman S

PY - 2006/11

Y1 - 2006/11

N2 - The proteasome is an essential evolutionary conserved protease involved in many regulatory systems. Here, we describe the synthesis and characterization of the activity-based, fluorescent, and cell-permeable inhibitor Bodipy TMR-Ahx(3)L(3)VS (MV151), which specifically targets all active subunits of the proteasome and immunoproteasome in living cells, allowing for rapid and sensitive in-gel detection. The inhibition profile of a panel of commonly used proteasome inhibitors could be readily determined by MV151 labeling. Administration of MV151 to mice allowed for in vivo labeling of proteasomes, which correlated with inhibition of proteasomal degradation in the affected tissues. This probe can be used for many applications ranging from clinical profiling of proteasome activity, to biochemical analysis of subunit specificity of inhibitors, and to cell biological analysis of the proteasome function and dynamics in living cells.

AB - The proteasome is an essential evolutionary conserved protease involved in many regulatory systems. Here, we describe the synthesis and characterization of the activity-based, fluorescent, and cell-permeable inhibitor Bodipy TMR-Ahx(3)L(3)VS (MV151), which specifically targets all active subunits of the proteasome and immunoproteasome in living cells, allowing for rapid and sensitive in-gel detection. The inhibition profile of a panel of commonly used proteasome inhibitors could be readily determined by MV151 labeling. Administration of MV151 to mice allowed for in vivo labeling of proteasomes, which correlated with inhibition of proteasomal degradation in the affected tissues. This probe can be used for many applications ranging from clinical profiling of proteasome activity, to biochemical analysis of subunit specificity of inhibitors, and to cell biological analysis of the proteasome function and dynamics in living cells.

KW - Animals

KW - Boron Compounds

KW - Cell Line, Tumor

KW - Fluorescent Dyes

KW - Humans

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Oligopeptides

KW - Protease Inhibitors

KW - Proteasome Endopeptidase Complex

KW - Proteasome Inhibitors

U2 - 10.1016/j.chembiol.2006.09.013

DO - 10.1016/j.chembiol.2006.09.013

M3 - Article

C2 - 17114003

SN - 1074-5521

VL - 13

SP - 1217

EP - 1226

JO - Chemistry & Biology

JF - Chemistry & Biology

IS - 11

ER -

A fluorescent broad-spectrum proteasome inhibitor for labeling proteasomes in vitro and in vivo

Abstract

Keywords

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