Inhibition of NF-kappaB activation by a dominant-negative mutant of IkappaBalpha.
The activity of the transcription factor NF-kappaB is tightly regulated by the inhibitory molecule IkappaBalpha. Upon stimulation, IkappaBalpha is rapidly degraded and NF-kappaB translocates to the nucleus to induce gene expression. The IkappaBalpha degradation is preceded by phosphorylation, suggesting that this event plays a role in the activation of NF-kappaB. In this study, we have mutated three potential phosphorylation sites in porcine IkappaBalpha and found that expression of the Ser32 mutant of IkappaBalpha (IS32A), but not Tyr42 or Ser262 mutants or wild-type IkappaBalpha, blocked the activation of NF-kappaB by TNF-alpha. These results suggest that the Ser32 residue, a potential casein kinase II phosphorylation site, is critical for NF-kappaB activation.
Chen
C G
CG
Immunology Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia.
Malliaros
J
J
Katerelos
M
M
d'Apice
A J
AJ
Pearse
M J
MJ
D000818:Animals; D047390:Casein Kinase II; D005799:Genes, Dominant; D051379:Mice; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins; D013552:Swine; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014158:Transcription, Genetic
D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases