Transcriptional regulation by the proteasome as a mechanism for cellular protein homeostasis.

Protein degradation mediated by the ubiquitin-proteasome system is a vitally important means of regulation for many cellular processes. An increasing body of evidence implicates the proteasome in the regulation of gene transcription through a variety of mechanisms, including transcription factor processing and proteasome-chromatin association. Recently a genomic approach was used to elucidate the transcriptional effects of the proteasome in budding yeast. Results indicate a positive role for proteasome activity in the transcription of several functional gene classes, including the ribosomal protein genes. In addition, proteasome activity was found to be required for the expression of Spt23 target genes, independent of the proteasomal processing of this transcription factor, suggesting cooperativity between two forms of transcriptional regulation by the proteasome. Here we discuss several implications of these findings, including a possible feedback mechanism between protein synthesis and protein degradation via the transcriptional regulation of ribosomal protein genes by the proteasome.