SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation.
Activation of NF-kappaB is achieved by ubiquitination and proteasome-mediated degradation of IkappaBalpha. We have detected modified IkappaBalpha, conjugated to the small ubiquitin-like protein SUMO-1, which is resistant to signal-induced degradation. In the presence of an E1 SUMO-1-activating enzyme, Ubch9 conjugated SUMO-1 to IkappaBalpha primarily on K21, which is also utilized for ubiquitin modification. Thus, SUMO-1-modified IkappaBalpha cannot be ubiquitinated and is resistant to proteasome-mediated degradation. As a result, overexpression of SUMO-1 inhibits signal-induced activation of NF-kappaB-dependent transcription. Unlike ubiquitin modification, which requires phosphorylation of S32 and S36, SUMO-1 modification of IkappaBalpha is inhibited by phosphorylation. Thus, while ubiquitination targets proteins for rapid degradation, SUMO-1 modification acts antagonistically to generate proteins resistant to degradation.
Pubmed ID: 9734360 RIS Download
Amino Acid Sequence | Animals | Base Sequence | Binding Sites | Cell Line | Cysteine Endopeptidases | DNA, Recombinant | DNA-Binding Proteins | Humans | I-kappa B Proteins | Interleukin-1 | Macromolecular Substances | Multienzyme Complexes | NF-kappa B | Proteasome Endopeptidase Complex | Recombinant Proteins | SUMO-1 Protein | Signal Transduction | Transcriptional Activation | Tumor Necrosis Factor-alpha | Ubiquitins