LMP2-Specific Inhibitors: Chemical Genetic Tools for Proteasome Biology

Yik Khuan (Abby) Ho; Paola Bargagna-Mohan; Marie Wehenkel; Royce Mohan; Kyung Bo Kim

doi:10.1016/j.chembiol.2007.03.008

LMP2-Specific Inhibitors: Chemical Genetic Tools for Proteasome Biology

Yik Khuan (Abby) Ho, Paola Bargagna-Mohan, Marie Wehenkel, Royce Mohan, Kyung Bo Kim

Pharmaceutical Sciences

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

94 Scopus citations

Abstract

The immunoproteasome, having been linked to neurodegenerative diseases and hematological cancers, has been shown to play an important role in MHC class I antigen presentation. However, its other pathophysiological functions are still not very well understood. This can be attributed mainly to a lack of appropriate molecular probes that can selectively modulate the immunoproteasome catalytic subunits. Herein, we report the development of molecular probes that selectively inhibit the major catalytic subunit, LMP2, of the immunoproteasome. We show that these compounds irreversibly modify the LMP2 subunit with high specificity. Importantly, LMP2-rich cancer cells compared to LMP2-deficient cancer cells are more sensitive to growth inhibition by the LMP2-specific inhibitor, implicating an important role of LMP2 in regulating cell growth of malignant tumors that highly express LMP2.

Original language	English
Pages (from-to)	419-430
Number of pages	12
Journal	Chemistry and Biology
Volume	14
Issue number	4
DOIs	https://doi.org/10.1016/j.chembiol.2007.03.008
State	Published - Apr 20 2007

Bibliographical note

Funding Information:
We are grateful to the Kentucky Lung Cancer Research Program (K.-B.K), for Kentucky Tobacco Research and Development Center grants, for a Research to Prevent Blindness Challenge grant (R.M.), and for the financial support of a University of Kentucky Graduate School Fellowship (Y.K.H.).

Keywords

CHEMBIOL
MOLIMMUNO

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chembiol.2007.03.008

Cite this

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title = "LMP2-Specific Inhibitors: Chemical Genetic Tools for Proteasome Biology",

abstract = "The immunoproteasome, having been linked to neurodegenerative diseases and hematological cancers, has been shown to play an important role in MHC class I antigen presentation. However, its other pathophysiological functions are still not very well understood. This can be attributed mainly to a lack of appropriate molecular probes that can selectively modulate the immunoproteasome catalytic subunits. Herein, we report the development of molecular probes that selectively inhibit the major catalytic subunit, LMP2, of the immunoproteasome. We show that these compounds irreversibly modify the LMP2 subunit with high specificity. Importantly, LMP2-rich cancer cells compared to LMP2-deficient cancer cells are more sensitive to growth inhibition by the LMP2-specific inhibitor, implicating an important role of LMP2 in regulating cell growth of malignant tumors that highly express LMP2.",

keywords = "CHEMBIOL, MOLIMMUNO",

author = "Ho, {Yik Khuan (Abby)} and Paola Bargagna-Mohan and Marie Wehenkel and Royce Mohan and Kim, {Kyung Bo}",

note = "Funding Information: We are grateful to the Kentucky Lung Cancer Research Program (K.-B.K), for Kentucky Tobacco Research and Development Center grants, for a Research to Prevent Blindness Challenge grant (R.M.), and for the financial support of a University of Kentucky Graduate School Fellowship (Y.K.H.).",

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AU - Ho, Yik Khuan (Abby)

AU - Bargagna-Mohan, Paola

AU - Wehenkel, Marie

AU - Mohan, Royce

AU - Kim, Kyung Bo

N1 - Funding Information: We are grateful to the Kentucky Lung Cancer Research Program (K.-B.K), for Kentucky Tobacco Research and Development Center grants, for a Research to Prevent Blindness Challenge grant (R.M.), and for the financial support of a University of Kentucky Graduate School Fellowship (Y.K.H.).

PY - 2007/4/20

Y1 - 2007/4/20

N2 - The immunoproteasome, having been linked to neurodegenerative diseases and hematological cancers, has been shown to play an important role in MHC class I antigen presentation. However, its other pathophysiological functions are still not very well understood. This can be attributed mainly to a lack of appropriate molecular probes that can selectively modulate the immunoproteasome catalytic subunits. Herein, we report the development of molecular probes that selectively inhibit the major catalytic subunit, LMP2, of the immunoproteasome. We show that these compounds irreversibly modify the LMP2 subunit with high specificity. Importantly, LMP2-rich cancer cells compared to LMP2-deficient cancer cells are more sensitive to growth inhibition by the LMP2-specific inhibitor, implicating an important role of LMP2 in regulating cell growth of malignant tumors that highly express LMP2.

AB - The immunoproteasome, having been linked to neurodegenerative diseases and hematological cancers, has been shown to play an important role in MHC class I antigen presentation. However, its other pathophysiological functions are still not very well understood. This can be attributed mainly to a lack of appropriate molecular probes that can selectively modulate the immunoproteasome catalytic subunits. Herein, we report the development of molecular probes that selectively inhibit the major catalytic subunit, LMP2, of the immunoproteasome. We show that these compounds irreversibly modify the LMP2 subunit with high specificity. Importantly, LMP2-rich cancer cells compared to LMP2-deficient cancer cells are more sensitive to growth inhibition by the LMP2-specific inhibitor, implicating an important role of LMP2 in regulating cell growth of malignant tumors that highly express LMP2.

KW - CHEMBIOL

KW - MOLIMMUNO

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M3 - Article

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AN - SCOPUS:34247190754

SN - 1074-5521

VL - 14

SP - 419

EP - 430

JO - Chemistry and Biology

JF - Chemistry and Biology

IS - 4

ER -

LMP2-Specific Inhibitors: Chemical Genetic Tools for Proteasome Biology

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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