Proteasomal activity suppression

Yin, L., Laevsky, G., Giardina, C. 2001. Butyrate suppression of colonocyte NF-kB activation and cellular proteasome activity. 1. Biol. Chem. 276, 44641-44646. 

Lin, J. K., Chen, Y. W., and Lin-Shiau, S. Y. 2006. Inhibition of breast cancer cell proliferation by theaflavins from black tea through suppressing proteasomal activities. Proc. AACR 47 538-39. 

Inhibition of Breast Cancer Cell Proliferation by Theaflavins and Epigallocatechin 3-gallate through Suppressing Proteasomal Activities... 

The use of different classes of natural product-based proteasome inhibitors as molecular probes has revealed that just as each structural class reacts with the proteolytic sites within the 20S proteasome through a distinct chemical mechanism, each class of inhibitor also exhibits a unique pattern of active site selectivity and protein specificity. Therefore, natural products and other small molecule proteasome inhibitors have not only proved to be invaluable probes to study proteasome function, but have also been valuable tools to examine the diversity of pharmacological/cellular responses produced by selective (or in some cases relatively nonselective) suppression of distinctly different catalytic sites within the eukaryotic 26S proteasome. 

Stimuli such as tumor necrosis factor (TNF), chemotherapy, and irradiation. The activation of NF-kB involves the proteasome-dependent degradation of an inhibitor of NF-kB and results in a cascade of events leading to the suppression of apoptosis. 

The proteasome has been implicated as a key player in a number of important cellular processes including apoptosis, cell differentiation, MHC class I antigen presentation, NF-xB activation, tumor suppression, and cell division. In particular, the prominent role that the proteasome plays in cellular proliferation has generated much attention toward the use of proteasome inhibitors as antitumor chemotherapeutic agents. As more and more cellular functions are linked to the proteasome, the use of proteasome inhibitors will be increasingly important in the investigation of various signaling interactions. 

G.P., and Dou, Q.P. (2007) Qioquinol, a therapeutic agent for Alzheimer s disease, has proteasome-inhibitory, androgen receptor-suppressing, apoptosis-inducing, and antitumor activities in human prostate cancer cells and xenografts. 

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