The gene encoding the 105-kDa protein (p105) precursor of the p50 subunit of transcription factor NF-κB also encodes a p70IκB protein, IκBγ which is identical to the C-terminal 607 amino acids of p105. Here we show that alternative RNA splicing generates IκBγ isoforms with properties different from those of p70. One 63-kDa isoform, termed IκBγ-1, which lacks 59 amino acids C-terminal to ankyrin repeat 7, has a novel 35-amino acid C terminus encoded by an alternative reading frame of the p105 gene. A 55-kDa isoform, IκBγ-2, lacks the 190 C-terminal amino acids of p70IκBγ. In contrast to p70IκBγ, which is a cytoplasmic protein, IκBγ-1 is found in both the cytoplasm and nucleus, whereas IκBγ-2 is predominantly nuclear. The IκBγ isoforms also display differences in specificity and affinity for Rel/NF-κB proteins. While p70IκBγ inhibits p50-, p65-, and c-Rel-mediated transactivation and/or DNA binding, both IκBγ-1 and IκBγ-2 are specific for p50 and have different affinities for this subunit. The absence in IκBγ-1 and IκBγ-2 of a protein kinase A site whose phosphorylation modulates p70IκBγ inhibitory activity suggests that alternative RNA splicing may be used to generate IκBγ isoforms that respond differently to intracellular signals.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 10 May 1994|
- RNA splicing
- transcription factors