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Ubiquitin Receptor Rpn13 Mediates The Inhibitory Interaction Of Diphenyldihaloketones Clefma And Ef24 With The 26s Proteasome, Geeta Rao, Gregory Nkepang, Jian Xu, Hooman Yari, Hailey Houson, Chengwen Teng Pharm.D., Ph.D., Vibhudutta Awasthi

Faculty Publications

The proteasome is a validated target in drug discovery for diseases associated with unusual proteasomal activity. Here we report that two diphenyldihaloketones, CLEFMA and EF24, inhibit the peptidase activity of the 26S proteasome. The objective of this study was to investigate interaction of these compounds with the proteasome and identify a putative target within the protein components of the 26S proteasome. We employed standard fluorogenic peptide-based proteasome activity assay for trypsin-like, chymotrypsin-like, and caspase-like activities of human purified 26S proteasome in cell-free conditions. GFPu-1 and HUVEC cells were used as proteasome reporter cells. Direct binding studies used purified 19S, 20S, …