Proteolytic degradation of the C-terminal region of NF-κB precursors to their active DNA binding forms represents an important regulatory step in the activation of NF-κB. NF-κB2(p100) is found ubiquitously in the cytoplasm; however, the site and mechanism of processing to p52 have not previously been defined. We show by deletion mapping that processing of NF-κB2(p100) terminates at alanine 405 to generate p52 and is prevented by specific inhibitors of the multicatalytic proteinase complex. Although the C-terminal IκB-like domain of NF-κB2(p100) was constitutively phosphorylated, disruption of this phosphorylation by mutagenesis demonstrated that it was not required as a signal to mediate processing. Mutational analysis further showed that cleavage of NF-κB2 is not dependent on a specific sequence motif adjacent to alanine 405, the ankyrin repeats, or other C-terminal sequences but is directed by structural determinants amino terminal to the cleavage site, within the Rel homology domain and/or the glycine hinge region. The level of processing of NF-κB2(p100) was much lower than that of NF- κB1(p105) and differed from that of IκB-α, suggesting differential control of processing of NF-κB/IκB family members.
|Original language||English (US)|
|Number of pages||9|
|Journal||Molecular and Cellular Biology|
|State||Published - 1996|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology