PHYSIOLOGICAL TURNOVER OF NUCLEAR FACTOR KAPPA-B BY NUCLEAR PROTEOLYSIS

Regenerating Liver is a physiologic animal system in which p50/p65 nuc lear factor kappa B (NF-KR) DNA binding activity is induced and rapidl y disappears in the remnant liver within minutes of partial hepatectom y. The activation of NF-kappa B may contribute to the mechanism by whi ch hepatocytes regulate their mitogenic program during liver regenerat ion. A p50/NF-kappa B1-p35/RelA heterodimer that contains a proteolyze d amino-terminal DNA binding fragment of p65/RelA is also present in t he nuclei of hepatic cells within minutes of partial hepatectomy. In t he absence of I kappa B-alpha resynthesis, turnover of NF-kappa B occu rs 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 prote olysis provides a potential mechanism for tightly regulating the level of active NF-kappa B.