p105 and p98 precursor proteins play an active role in NF-kappa B-mediated signal transduction.
The Rel/NF-kappa B family of transcription factors is composed of two distinct subgroups, proteins that undergo proteolytic processing and contain SWI6/ankyrin repeats in their carboxyl termini (p105, p98), and those without such repeats that do not require processing (p65, c-Rel, RelB, and Dorsal). We demonstrate that the p105 and p98 precursors share functional properties with the I kappa B proteins, which also contain SWI6/ankyrin repeats. Both p105 and p98 were found to form stable complexes with other Rel/NF-kappa B family members, including p65 and c-Rel. Association with the precursors is sufficient for cytoplasmic retention of either p65 or c-Rel, both of which are otherwise nuclear. These complexes undergo stimulus-responsive processing to produce active p50/c-Rel and p55/c-Rel complexes. These observations suggest a second pathway leading to NF-kappa B induction, in which processing of the precursors rather than phosphorylation of I kappa B plays a major role.
Mercurio
F
F
Department of Pharmacology, University of California, San Diego, School of Medicine, La Jolla 92093-0636.
DiDonato
J A
JA
Rosette
C
C
Karin
M
M
D000936:Antigen-Antibody Complex; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D011233:Precipitin Tests; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology*; D021382:Protein Sorting Signals / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology; D020569:Proto-Oncogene Proteins c-rel; D011519:Proto-Oncogenes; D015398:Signal Transduction / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000502:physiology*
D000936:Antigen-Antibody Complex; D046911:Macromolecular Substances; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011498:Protein Precursors; D021382:Protein Sorting Signals; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; C497593:RELB protein, human; D014157:Transcription Factors; D051841:Transcription Factor RelB