Abstract
Activation of NF-kappaB transcription factors requires phosphorylation and ubiquitin-proteasome-dependent degradation of IkappaB proteins. We provide evidence that a human F-box protein, h-betaTrCP, a component of Skp1-Cullin-F-box protein (SCF) complexes, a new class of E3 ubiquitin ligases, is essential for inducible degradation of IkappaBalpha. betaTrCP associates with Ser32-Ser36 phosphorylated, but not with unmodified IkappaBalpha or Ser32-Ser36 phosphorylation-deficient mutants. Expression of a F-box-deleted betaTrCP inhibits IkappaBalpha degradation, promotes accumulation of phosphorylated Ser32-Ser36 IkappaBalpha, and prevents NF-kappaB-dependent transcription. Our findings indicate that betaTrCP is the adaptor protein required for IkappaBalpha recognition by the SCFbetaTrCP E3 complex that ubiquitinates IkappaBalpha and makes it a substrate for the proteasome.
Original language | English |
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Pages (from-to) | 7941-5 |
Number of pages | 5 |
Journal | The Journal of Biological Chemistry |
Volume | 274 |
Issue number | 12 |
Publication status | Published - 19 Mar 1999 |
Keywords
- beta-Transducin Repeat-Containing Proteins
- NF-kappa B
- Cell Cycle Proteins
- HeLa Cells
- Peptide Synthases
- DNA-Binding Proteins
- Humans
- Transcription, Genetic
- GTP-Binding Proteins
- S-Phase Kinase-Associated Proteins
- SKP Cullin F-Box Protein Ligases
- Multienzyme Complexes
- Phosphorylation
- Cysteine Endopeptidases
- I-kappa B Proteins
- Proteasome Endopeptidase Complex
- Models, Chemical
- Serine