ALTERNATIVE SPLICING OF RNA TRANSCRIPTS ENCODED BY THE MURINE P105 NF-KAPPA-B GENE GENERATES I-KAPPA-B-GAMMA ISOFORMS WITH DIFFERENT INHIBITORY ACTIVITIES
- Author(s)
- Grumont, RJ; Gerondakis, S;
- Details
- Publication Year 1994-05-10,Volume 91,Issue #10,Page 4367-4371
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- The gene encoding the 105-kDa protein (p105) precursor of the p50 subunit of transcription factor NF-kappa B also encodes a p70 I kappa B protein, I kappa B gamma, which is identical to the C-terminal 607 amino acids of p105. Here we show that alternative RNA splicing generates I kappa B gamma isoforms with properties different from those of p70. One 63-kDa isoform, termed I kappa B gamma-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, I kappa B gamma-2, lacks the 190 C-terminal amino acids of p70I kappa B gamma. In contrast to p70I kappa B gamma, which is a cytoplasmic protein, I kappa B gamma-1 is found in both the cytoplasm and nucleus, whereas I kappa B gamma-2 is predominantly nuclear. The I kappa B gamma isoforms also display differences in specificity and affinity for Rel/NF-kappa B proteins. While p70I kappa B gamma inhibits p50-, p65-, and c-Rel-mediated transactivation and/or DNA binding, both I kappa B gamma-1 and I kappa B gamma-2 are specific for p50 and have different affinities for this subunit. The absence in I kappa B gamma-1 and I kappa B gamma-2 of a protein kinase A site whose phosphorylation modulates p70I kappa B gamma inhibitory activity suggests that alternative RNA splicing may be used to generate I kappa B gamma isoforms that respond differently to intracellular signals.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- DNA-BINDING; REL; PROTEIN; ACTIVATOR; DORSAL; SUBUNITS; REPEATS; P50
- Publisher's Version
- https://doi.org/10.1073/pnas.91.10.4367
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1994-05-10 12:00:00