Common structural constituents confer I kappa B activity to NF-kappa B p105 and I kappa B/MAD-3 - PubMed (original) (raw)

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

E N Hatada et al. EMBO J. 1993 Jul.

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.

PubMed Disclaimer

Similar articles

• Interaction of the C-terminal region of p105 with the nuclear localisation signal of p50 is required for inhibition of NF-kappa B DNA binding activity.
  Matthews JR, Watson E, Buckley S, Hay RT. Matthews JR, et al. Nucleic Acids Res. 1993 Sep 25;21(19):4516-23. doi: 10.1093/nar/21.19.4516. Nucleic Acids Res. 1993. PMID: 7694229 Free PMC article.
• 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.
  Hatada EN, Nieters A, Wulczyn FG, Naumann M, Meyer R, Nucifora G, McKeithan TW, Scheidereit C. Hatada EN, et al. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2489-93. doi: 10.1073/pnas.89.6.2489. Proc Natl Acad Sci U S A. 1992. PMID: 1532257 Free PMC article.
• The activity of a 70 kilodalton I kappa B molecule identical to the carboxyl terminus of the p105 NF-kappa B precursor is modulated by protein kinase A.
  Gerondakis S, Morrice N, Richardson IB, Wettenhall R, Fecondo J, Grumont RJ. Gerondakis S, et al. Cell Growth Differ. 1993 Aug;4(8):617-27. Cell Growth Differ. 1993. PMID: 8398903
• The inhibitory ankyrin and activator Rel proteins.
  Nolan GP, Baltimore D. Nolan GP, et al. Curr Opin Genet Dev. 1992 Apr;2(2):211-20. doi: 10.1016/s0959-437x(05)80276-x. Curr Opin Genet Dev. 1992. PMID: 1386268 Review.
• Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation.
  Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto S. Verma IM, et al. Genes Dev. 1995 Nov 15;9(22):2723-35. doi: 10.1101/gad.9.22.2723. Genes Dev. 1995. PMID: 7590248 Review. No abstract available.

Cited by

• IκΒα inhibits apoptosis at the outer mitochondrial membrane independently of NF-κB retention.
  Pazarentzos E, Mahul-Mellier AL, Datler C, Chaisaklert W, Hwang MS, Kroon J, Qize D, Osborne F, Al-Rubaish A, Al-Ali A, Mazarakis ND, Aboagye EO, Grimm S. Pazarentzos E, et al. EMBO J. 2014 Dec 1;33(23):2814-28. doi: 10.15252/embj.201488183. Epub 2014 Oct 31. EMBO J. 2014. PMID: 25361605 Free PMC article.
• Polydnavirus Ank proteins bind NF-κB homodimers and inhibit processing of Relish.
  Bitra K, Suderman RJ, Strand MR. Bitra K, et al. PLoS Pathog. 2012;8(5):e1002722. doi: 10.1371/journal.ppat.1002722. Epub 2012 May 24. PLoS Pathog. 2012. PMID: 22654665 Free PMC article.
• NF-κB regulation: lessons from structures.
  Ghosh G, Wang VY, Huang DB, Fusco A. Ghosh G, et al. Immunol Rev. 2012 Mar;246(1):36-58. doi: 10.1111/j.1600-065X.2012.01097.x. Immunol Rev. 2012. PMID: 22435546 Free PMC article. Review.
• LPS preconditioning redirects TLR signaling following stroke: TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury.
  Vartanian KB, Stevens SL, Marsh BJ, Williams-Karnesky R, Lessov NS, Stenzel-Poore MP. Vartanian KB, et al. J Neuroinflammation. 2011 Oct 14;8:140. doi: 10.1186/1742-2094-8-140. J Neuroinflammation. 2011. PMID: 21999375 Free PMC article.
• NF-kappaB activation in melanoma.
  Ueda Y, Richmond A. Ueda Y, et al. Pigment Cell Res. 2006 Apr;19(2):112-24. doi: 10.1111/j.1600-0749.2006.00304.x. Pigment Cell Res. 2006. PMID: 16524427 Free PMC article. Review.

References

1. 1. DNA Cell Biol. 1992 Sep;11(7):523-37 - PubMed
2. 1. Int Rev Cytol. 1993;143:1-62 - PubMed
3. 1. Arch Biochem Biophys. 1968 Jul;126(1):155-64 - PubMed
4. 1. Nature. 1970 Aug 15;227(5259):680-5 - PubMed
5. 1. Anal Biochem. 1980 Nov 15;109(1):76-86 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Europe PubMed Central
  • Nature Publishing Group
  • PubMed Central
  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations

• Research Materials

  • NCI CPTC Antibody Characterization Program