Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha

Mol Cell. 1999 Apr;3(4):527-33. doi: 10.1016/s1097-2765(00)80481-5.

Abstract

Activation of the transcription factor NF-kappa B in response to proinflammatory stimuli requires the phosphorylation-triggered and ubiquitin-dependent degradation of the NF-kappa B inhibitor, I kappa B alpha. Here, we show the in vitro reconstitution of the phosphorylation-dependent ubiquitination of I kappa B alpha with purified components. ROC1, a novel SCF-associated protein, is recruited by cullin 1 to form a quatemary SCFHOS-ROC1 holenzyme (with Skp1 and the beta-TRCP homolog HOS). SCFHOS-ROC1 binds IKK beta-phosphorylated I kappa B alpha and catalyzes its ubiquitination in the presence of ubiquitin, E1, and Cdc34. ROC1 plays a unique role in the ubiquitination reaction by heterodimerizing with cullin 1 to catalyze ubiquitin polymerization.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle Proteins / metabolism*
  • Cullin Proteins*
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Humans
  • I-kappa B Kinase
  • I-kappa B Proteins*
  • Molecular Sequence Data
  • NF-KappaB Inhibitor alpha
  • Peptide Synthases / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • S-Phase Kinase-Associated Proteins
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitins / metabolism

Substances

  • Cell Cycle Proteins
  • Cullin 1
  • Cullin Proteins
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • NFKBIA protein, human
  • S-Phase Kinase-Associated Proteins
  • Ubiquitins
  • NF-KappaB Inhibitor alpha
  • SKP Cullin F-Box Protein Ligases
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Peptide Synthases