A ROLE FOR PHOSPHORYLATION IN THE PROTEOLYTIC PROCESSING OF THE HUMANNF-KAPPA-B1 PRECURSOR

A precursor, p105, for one of the subunits (p50) of the NF-kappa B tra nscription factor, plays an important role in inducible expression of diverse cellular genes. p105 also functions as a cytoplasmic inhibitor for NF-kappa B, and the proteolytic processing of its inhibitory C-te rminal region is required for generation of active NF-kappa B. Here, i t is reported that the human p105 C-terminal region is phosphorylated in vivo on Ser(894) and Ser(908), which are potential phosphorylation sites in vitro for proline-directed serine/threonine kinases such as c yclin-dependent kinase. Furthermore, the mutation of these in vivo pho sphorylation sites retards p105 processing in vivo, suggesting that p1 05 processing is regulated in a phosphorylation-dependent manner.