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PMID: 8334994 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Common structural constituents confer I kappa B activity to NF-kappa B p105 and I kappa B/MAD-3.

The EMBO journal ·Vol. 12 ·No. 7 ·1993-07-00 ·Pages 2781-8

Hatada EN, Naumann M, Scheidereit C

Abstract

The vertebrate NF-kappa B/c-rel inhibitors MAD-3/I kappa B alpha, I kappa B gamma/pdI and bcl-3 all share a conserved ankyrin repeat domain (ARD) consisting of six complete repeats, a short acidic motif and/or an incomplete seventh repeat. We present here a detailed analysis of the domain in p105/pdI and MAD-3/I kappa B involved in inhibition of DNA binding and in protein interaction with rel factors. We demonstrate that in both cases an acidic region and six ankyrin-like repeats are sufficient and required for protein interaction with the rel factors. However, for p105/pdI to achieve the high affinity needed to suppress DNA binding, an incomplete seventh repeat is required in addition. Both pdI and MAD-3 associate with rel proteins by forming heterotrimeric complexes, as shown by native gel analysis and by cross-linking. Furthermore, we demonstrate that deletion of only three amino acids in the first repeat converts the subunit specificity of the p105 ARD into that of MAD-3/I kappa B. We conclude that functionally the ARD in these molecules has a modular structure, with different subregions determining the specificity for the NF-kappa B subunits p50 and p65.

MeSH Terms
Amino Acid Sequence Animals Ankyrins/chemistry Binding Sites DNA/metabolism DNA-Binding Proteins/chemistry,metabolism I-kappa B Proteins Molecular Sequence Data NF-KappaB Inhibitor alpha NF-kappa B/chemistry,metabolism NF-kappa B p50 Subunit Protein Precursors/chemistry,metabolism Proto-Oncogene Proteins/chemistry,metabolism Repetitive Sequences, Nucleic Acid Sequence Deletion Structure-Activity Relationship Transcription Factor RelB Transcription Factors Vertebrates
Chemicals
Ankyrins DNA-Binding Proteins I-kappa B Proteins NF-kappa B NF-kappa B p50 Subunit Protein Precursors Proto-Oncogene Proteins Transcription Factors NF-KappaB Inhibitor alpha Transcription Factor RelB DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hatada E N
Max-Planck-Institut für Molekulare Genetik, Otto-Warburg-Laboratorium, Berline (Dahlem), Germany.
Naumann M
Scheidereit C
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-07-00
Pages
2781-8
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413528
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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