RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: a negative feedback circuit

Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3056-61. doi: 10.1073/pnas.071022298.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Cell Division
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • G1 Phase
  • Gene Expression Regulation
  • Ligands
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Peptide Hydrolases / metabolism*
  • Proteasome Endopeptidase Complex
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins*
  • Substrate Specificity
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Ubiquitin / metabolism

Substances

  • DNA-Binding Proteins
  • Fungal Proteins
  • Ligands
  • Multienzyme Complexes
  • RNA-Binding Proteins
  • RNP1 protein, S cerevisiae
  • RPN4 protein, S cerevisiae
  • Ribonucleoproteins
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Ubiquitin
  • Peptide Hydrolases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease