Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome

Science. 2001 May 18;292(5520):1382-5. doi: 10.1126/science.1059780. Epub 2001 May 3.

Abstract

SCF ubiquitin ligases control various processes by marking regulatory proteins for ubiquitin-dependent proteolysis. To illuminate how SCF complexes are regulated, we sought proteins that interact with the human SCF component CUL1. The COP9 signalosome (CSN), a suppressor of plant photomorphogenesis, associated with multiple cullins and promoted cleavage of the ubiquitin-like protein NEDD8 from Schizosaccharomyces pombe CUL1 in vivo and in vitro. Multiple NEDD8-modified proteins uniquely accumulated in CSN-deficient S. pombe cells. We propose that the broad spectrum of activities previously attributed to CSN subunits--including repression of photomorphogenesis, activation of JUN, and activation of p27 nuclear export--underscores the importance of dynamic cycles of NEDD8 attachment and removal in biological regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Blotting, Western
  • COP9 Signalosome Complex
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cullin Proteins*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • HeLa Cells
  • Humans
  • Mass Spectrometry
  • Mice
  • Multiprotein Complexes
  • Mutation / genetics
  • NEDD8 Protein
  • Peptide Hydrolases
  • Peptide Synthases / metabolism
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein Subunits
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • SKP Cullin F-Box Protein Ligases
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Substrate Specificity
  • Swine
  • Transfection
  • Two-Hybrid System Techniques
  • Ubiquitins / genetics
  • Ubiquitins / metabolism*

Substances

  • Cell Cycle Proteins
  • Cullin 1
  • Cullin Proteins
  • Fungal Proteins
  • Multiprotein Complexes
  • NEDD8 Protein
  • NEDD8 protein, human
  • Nedd8 protein, mouse
  • Protein Subunits
  • Proteins
  • Recombinant Fusion Proteins
  • Ubiquitins
  • SKP Cullin F-Box Protein Ligases
  • Peptide Hydrolases
  • COP9 Signalosome Complex
  • Peptide Synthases