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.
|Number of pages||12|
|Journal||Chemistry and Biology|
|State||Published - Apr 20 2007|
Bibliographical noteFunding 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
- Molecular Medicine
- Molecular Biology
- Drug Discovery
- Clinical Biochemistry