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. In addition to the proteasome genes, Rpn4 regulates numerous other genes involved in a wide variety of cellular processes. However, the transcription activation domain of Rpn4 remains largely unclear. Here we locate a major transactivation domain of Rpn4 in the N-terminal region between residues 118 and 210. Interestingly, this domain is separate from its degradation signals (degrons), suggesting that functional overlap of sequences that activate transcription and signal degradation may not be as common as previously thought. We further demonstrate that the intracellular proteasome activity is correlated with the transactivation potency of Rpn4. This study provides important information for further understanding the biological functions of Rpn4 and the proteasome system.
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