Modulation of NF-kappaB activity by exchange of dimers.
Transcription factors within a family usually share the ability to recognize similar or identical consensus sites. For example, the five mammalian NF-kappaB/Rel proteins generate more than 12 dimers recognizing 9-11 nucleotide kappaB sites. Each dimer selectively regulates a few target promoters; however, several genes are redundantly induced by more than one dimer. Whether this property simply generates redundancy in target gene activation or underlies more complex regulatory mechanisms is an open issue. We show here that during dendritic cell maturation, rapidly activated dimers (e.g., p50/RelA) bound to a subset of target promoters are gradually replaced by slowly activated dimers (e.g., p52/RelB). Since the dimers have different transcriptional activity at each promoter, the dimer exchange allows fine tuning of the response over time. Further, due to the insensitivity of p52/RelB to the NF-kappaB inhibitors, the IkappaBs, dimer exchange contributes to sustained activation of selected NF-kappaB targets in spite of the resynthesis of IkappaBalpha.
Saccani
Simona
S
Institute for Research in Biomedicine, Via Vela 6, CH6500 Bellinzona, Switzerland.
Pantano
Serafino
S
Natoli
Gioacchino
G
D000256:Adenoviridae / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D007700:Kinetics; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020672:I-kappa B Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12