title: Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha.
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.
authors.affiliation: Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: P
authors.initials: P
authors.lastname: Tan
authors.forename: S Y
authors.initials: SY
authors.lastname: Fuchs
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Wu
authors.forename: C
authors.initials: C
authors.lastname: Gomez
authors.forename: Z
authors.initials: Z
authors.lastname: Ronai
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Pan
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism*; D044842:Cullin Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D010453:Peptide Synthases / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins; D044843:SKP Cullin F-Box Protein Ligases; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D044786:S-Phase Kinase-Associated Proteins; D014452:Ubiquitins; D000072000:NF-KappaB Inhibitor alpha; D044843:SKP Cullin F-Box Protein Ligases; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D010453:Peptide Synthases