Inducible degradation of Ikappa Balpha by the proteasome requires interaction with the F-box protein h-beta TrCP

Kroll, M., Margottin, F., Kohl, A. , Renard, P., Durand, H., Concordet, J., Bachelerie, F., Arenzana-Seisdedos, F. and Benarous, R. (1999) Inducible degradation of Ikappa Balpha by the proteasome requires interaction with the F-box protein h-beta TrCP. Journal of Biological Chemistry, 274(12), pp. 7941-7945. (doi: 10.1074/jbc.274.12.7941)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kohl, Professor Alain
• Authors: Kroll, M., Margottin, F., Kohl, A., Renard, P., Durand, H., Concordet, J., Bachelerie, F., Arenzana-Seisdedos, F., and Benarous, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Journal of Biological Chemistry
• Journal Abbr.: J. Biol. Chem
• Publisher: American Society for Biochemistry and Molecular Biology, Inc.
• ISSN: 0021-9258
• ISSN (Online): 1083-351X