Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP

M Kroll, F Margottin, A Kohl, P Renard, H Durand, J P Concordet, F Bachelerie, F Arenzana-Seisdedos, R Benarous

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)7941-5
Number of pages5
JournalThe Journal of Biological Chemistry
Volume274
Issue number12
Publication statusPublished - 19 Mar 1999

Fingerprint

beta-Transducin Repeat-Containing Proteins
F-Box Proteins
Proteasome Endopeptidase Complex
Degradation
Phosphorylation
NF-kappa B
SKP Cullin F-Box Protein Ligases
Ubiquitin-Protein Ligases
Transcription
Ubiquitin
Proteins
Transcription Factors
Chemical activation
Proteolysis
NF-KappaB Inhibitor alpha
Substrates

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

Cite this

Kroll, M., Margottin, F., Kohl, A., Renard, P., Durand, H., Concordet, J. P., ... Benarous, R. (1999). Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP. The Journal of Biological Chemistry, 274(12), 7941-5.
Kroll, M ; Margottin, F ; Kohl, A ; Renard, P ; Durand, H ; Concordet, J P ; Bachelerie, F ; Arenzana-Seisdedos, F ; Benarous, R. / Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP. In: The Journal of Biological Chemistry. 1999 ; Vol. 274, No. 12. pp. 7941-5.
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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.",
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Kroll, M, Margottin, F, Kohl, A, Renard, P, Durand, H, Concordet, JP, Bachelerie, F, Arenzana-Seisdedos, F & Benarous, R 1999, 'Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP', The Journal of Biological Chemistry, vol. 274, no. 12, pp. 7941-5.

Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP. / Kroll, M; Margottin, F; Kohl, A; Renard, P; Durand, H; Concordet, J P; Bachelerie, F; Arenzana-Seisdedos, F; Benarous, R.

In: The Journal of Biological Chemistry, Vol. 274, No. 12, 19.03.1999, p. 7941-5.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP

AU - Kroll, M

AU - Margottin, F

AU - Kohl, A

AU - Renard, P

AU - Durand, H

AU - Concordet, J P

AU - Bachelerie, F

AU - Arenzana-Seisdedos, F

AU - Benarous, R

PY - 1999/3/19

Y1 - 1999/3/19

N2 - 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.

AB - 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.

KW - beta-Transducin Repeat-Containing Proteins

KW - NF-kappa B

KW - Cell Cycle Proteins

KW - HeLa Cells

KW - Peptide Synthases

KW - DNA-Binding Proteins

KW - Humans

KW - Transcription, Genetic

KW - GTP-Binding Proteins

KW - S-Phase Kinase-Associated Proteins

KW - SKP Cullin F-Box Protein Ligases

KW - Multienzyme Complexes

KW - Phosphorylation

KW - Cysteine Endopeptidases

KW - I-kappa B Proteins

KW - Proteasome Endopeptidase Complex

KW - Models, Chemical

KW - Serine

M3 - Article

C2 - 10075690

VL - 274

SP - 7941

EP - 7945

JO - The Journal of Biological Chemistry

JF - The Journal of Biological Chemistry

SN - 0021-9258

IS - 12

ER -