Degradation of promoter-bound p65/RelA is essential for the prompt termination of the nuclear factor kappaB response.
Transcription factors of the nuclear factor (NF)-kappaB/Rel family translocate into the nucleus upon degradation of the IkappaBs. Postinduction repression of NF-kappaB activity depends on NF-kappaB-regulated resynthesis of IkappaBalpha, which dissociates NF-kappaB from DNA and exports it to the cytosol. We found that after activation, p65/RelA is degraded by the proteasome in the nucleus and in a DNA binding-dependent manner. If proteasome activity is blocked, NF-kappaB is not promptly removed from some target genes in spite of IkappaBalpha resynthesis and sustained transcription occurs. These results indicate that proteasomal degradation of p65/RelA does not merely regulate its stability and abundance, but also actively promotes transcriptional termination.
Saccani
Simona
S
Institute for Research in Biomedicine, Via Vela 6, 6500 Bellinzona, Switzerland.
Marazzi
Ivan
I
Beg
Amer A
AA
Natoli
Gioacchino
G
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism
D020672:I-kappa B Proteins; D009097:Multienzyme Complexes; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D051996:Transcription Factor RelA; D025801:Ubiquitin; D000072000:NF-KappaB Inhibitor alpha; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex