Abstract
The RPN4 (SON1, UFD5) protein of the yeast Saccharomyces cerevisiae is required for normal levels of intracellular proteolysis. RPN4 is a transcriptional activator of genes encoding proteasomal subunits. Here we show that RPN4 is required for normal levels of these subunits. Further, we demonstrate that RPN4 is extremely short-lived (t(1/2) approximately 2 min), that it directly interacts with RPN2, a subunit of the 26S proteasome, and that rpn4Delta cells are perturbed in their cell cycle. The degradation signal of RPN4 was mapped to its N-terminal region, outside the transcription-activation domains of RPN4. The ability of RPN4 to augment the synthesis of proteasomal subunits while being metabolically unstable yields a negative feedback circuit in which the same protein up-regulates the proteasome production and is destroyed by the assembled active proteasome.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites
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Cell Division
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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G1 Phase
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Gene Expression Regulation
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Ligands
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Multienzyme Complexes / genetics
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Multienzyme Complexes / metabolism
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Peptide Hydrolases / metabolism*
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Proteasome Endopeptidase Complex
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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Ribonucleoproteins
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Ribosomal Proteins / genetics
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Ribosomal Proteins / metabolism
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Saccharomyces cerevisiae
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Saccharomyces cerevisiae Proteins*
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Substrate Specificity
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Ubiquitin / metabolism
Substances
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DNA-Binding Proteins
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Fungal Proteins
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Ligands
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Multienzyme Complexes
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RNA-Binding Proteins
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RNP1 protein, S cerevisiae
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RPN4 protein, S cerevisiae
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Ribonucleoproteins
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Ribosomal Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Ubiquitin
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Peptide Hydrolases
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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ATP dependent 26S protease