RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: a negative feedback circuit.
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.
Mesh Terms:
Binding Sites, Cell Division, Cysteine Endopeptidases, DNA-Binding Proteins, Fungal Proteins, G1 Phase, Gene Expression Regulation, Ligands, Multienzyme Complexes, Peptide Hydrolases, Proteasome Endopeptidase Complex, RNA-Binding Proteins, Ribonucleoproteins, Ribosomal Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Substrate Specificity, Transcription Factors, Ubiquitin
Binding Sites, Cell Division, Cysteine Endopeptidases, DNA-Binding Proteins, Fungal Proteins, G1 Phase, Gene Expression Regulation, Ligands, Multienzyme Complexes, Peptide Hydrolases, Proteasome Endopeptidase Complex, RNA-Binding Proteins, Ribonucleoproteins, Ribosomal Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Substrate Specificity, Transcription Factors, Ubiquitin
Proc. Natl. Acad. Sci. U.S.A.
Date: Mar. 13, 2001
PubMed ID: 11248031
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