Disruption of Rpn4-Induced Proteasome Expression in Saccharomyces cerevisiae Reduces Cell Viability Under Stressed Conditions

Abstract

The proteasome homeostasis in Saccharomyces cerevisiae is regulated by a negative feedback circuit in which the transcription activator Rpn4 upregulates the proteasome genes and is rapidly degraded by the assembled proteasome. Previous studies have shown that rpn4Δ cells are sensitive to a variety of stresses. However, the contribution of the loss of Rpn4-induced proteasome expression to the rpn4Δ phenotypes remains unclear because Rpn4 controls numerous genes other than the proteasome genes. Here we construct a yeast strain in which one of the essential proteasome genes, PRE1, is no longer induced by Rpn4. We show that the active proteasome level is lower in this strain than in the wild-type counterpart. Moreover, we demonstrate that loss of Rpn4-induced proteasome expression leads to cell-cycle delay in G₂/M and sensitizes cells to various stresses. To our knowledge, this is the first report that explicitly reveals the physiological function of Rpn4-induced proteasome expression. This study also provides a tool for understanding the interactions between proteasome homeostasis and other cellular processes.