Rpn4p is a positive and negative transcriptional regulator of the ubiquitin-proteasome system

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Abstract

In eukaryotes, the ubiquitin-proteasome proteolytic system is involved in metabolizing most of cell proteins and in major regulation pathways. Although its structure and functioning are fairly well studied, little is known about the regulation of gene expression in this system. The regulation of proteasome gene expression has been described only for Saccharomyces cerevisiae and includes the proteasome-associated transcription factor Rpn4p and its binding site, the proteasome-associated control element (PACE). There are two questions concerning the role of Rpn4p as a transcription factor: whether Rpn4p regulates the PACE-containing genes of the protein ubiquitination system and what contribution Rpn4p makes to the stress-induced changes in proteasome mRNA levels. Semiquantitative RT-PCR showed that deletion of S. cerevisiae RPN4 decreased the RAD6, RAD23, and CDC48 mRNA levels, while the UBI4 mRNA level increased. Stress factors, such as heat shock or the alkylating agent methyl methanesulfonate, induced Rpn4p-dependent transcriptional upregulation of RPT4 and RPN5. At the same time, methyl methanesulfonate downregulated the CDC48 expression in the wild-type strain. Apparently, Rpn4p acts both as an activator and a repressor of transcription of the ubiquitinproteasome genes under normal and stress conditions.

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