PHYSIOLOGICAL 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-KR) 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.