A role for phosphorylation in the proteolytic processing of the human NF-kappa B1 precursor.

A precursor, p105, for one of the subunits (p50) of the NF-kappa B transcription 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-terminal region is required for generation of active NF-kappa B. Here, it is reported that the human p105 C-terminal region is phosphorylated in vivo on Ser894 and Ser908, which are potential phosphorylation sites in vitro for proline-directed serine/threonine kinases such as cyclin-dependent kinase. Furthermore, the mutation of these in vivo phosphorylation sites retards p105 processing in vivo, suggesting that p105 processing is regulated in a phosphorylation-dependent manner.