Feedback regulation of proteasome gene expression and its implications in cancer therapy.

Proteasomal protein degradation is one of the major regulatory mechanisms in the cell. Aberrant proteasome activity is directly related to the pathogenesis of many human diseases including cancers. How proteasome homeostasis is controlled is a fundamental question toward our understanding of proteasome dysregulation in cancer cells. The recent discovery of the Rpn4-proteasome negative feedback circuit provides mechanistic insight into the regulation of proteasome gene expression. This finding also has important implications in cancer therapy that uses small molecule inhibitors to target the proteasome.