Physiologic turnover of nuclear factor kappa B by nuclear proteolysis.
Regenerating liver is a physiologic animal system in which p50/p65 nuclear factor kappa B (NF-kappa B) DNA binding activity is induced and rapidly disappears in the remnant liver within minutes of partial hepatectomy. The activation of NF-kappa B may contribute to the mechanism by which hepatocytes regulate their mitogenic program during liver regeneration. A p50/NF-kappa B1-p35/RelA heterodimer that contains a proteolyzed amino-terminal DNA binding fragment of p65/RelA is also present in the nuclei of hepatic cells within minutes of partial hepatectomy. In the absence of I kappa B-alpha resynthesis, turnover of NF-kappa B occurs via conversion of p50/NF-kappa B1-p65/RelA to a p50/NF-kappa B1-p35/RelA DNA binding complex. Proteolytic conversion of p65/RelA into p35/RelA and subsequent degradation of p35/RelA account at least in part for the rapid turnover of NF-kappa B in the cell nuclei. Nuclear proteolysis provides a potential mechanism for tightly regulating the level of active NF-kappa B.
Cressman
D E
DE
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6145.
Taub
R
R
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006498:Hepatectomy; D006868:Hydrolysis; D020672:I-kappa B Proteins; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D012045:Regulatory Sequences, Nucleic Acid; D051996:Transcription Factor RelA
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA