LMP2-Specific Inhibitors: Chemical Genetic Tools for Proteasome Biology

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

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


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 languageEnglish
Pages (from-to)419-430
Number of pages12
JournalChemistry and Biology
Issue number4
StatePublished - 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.).



ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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