The ankyrin repeat domains of the NF-kappa B precursor p105 and the protooncogene bcl-3 act as specific inhibitors of NF-kappa B DNA binding.
The inducible pleiotropic transcription factor NF-kappa B is composed of two subunits, p50 and p65. The p50 subunit is encoded on the N-terminal half of a 105-kDa open reading frame and contains a rel-like domain. To date, no function has been described for the C-terminal portion. We show here that the C-terminal half of p105, when expressed as a separate molecule, binds to p50 and can rapidly disrupt protein-DNA complexes of p50 or native NF-kappa B. Deletion analysis of this precursor-derived inhibitor activity indicated a domain containing ankyrin-like repeats as necessary for inhibition. The protooncogene bcl-3, which contains seven ankyrin repeats, can equally inhibit p50 DNA binding. These observations identify bcl-3 as an inhibitor of NF-kappa B and strongly suggest that the ankyrin repeats in these factors are involved in protein-protein interactions with the rel-like domain of p50. Comparison with other ankyrin repeat-containing proteins suggests that a subclass of these proteins acts as regulators of rel-like transcription factors.
Hatada
E N
EN
Max-Planck-Institut fuer Molekulare Genetik, Otto-Warburg-Laboratorium, Berlin-Dahlem, Federal Republic of Germany.
Nieters
A
A
Wulczyn
F G
FG
Naumann
M
M
Meyer
R
R
Nucifora
G
G
McKeithan
T W
TW
Scheidereit
C
C
D000595:Amino Acid Sequence; D017487:Ankyrins; D000081242:B-Cell Lymphoma 3 Protein; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors
D017487:Ankyrins; D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D001798:Blood Proteins; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors