Common structural constituents confer I kappa B activity to NF-kappa B p105 and I kappa B/MAD-3
- PMID: 8334994
- PMCID: PMC413528
- DOI: 10.1002/j.1460-2075.1993.tb05939.x
Common structural constituents confer I kappa B activity to NF-kappa B p105 and I kappa B/MAD-3
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.
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.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.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.Cell Growth Differ. 1993 Aug;4(8):617-27. Cell Growth Differ. 1993. PMID: 8398903
-
The inhibitory ankyrin and activator Rel proteins.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.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
-
Phosphorylation of human I kappa B-alpha on serines 32 and 36 controls I kappa B-alpha proteolysis and NF-kappa B activation in response to diverse stimuli.EMBO J. 1995 Jun 15;14(12):2876-83. doi: 10.1002/j.1460-2075.1995.tb07287.x. EMBO J. 1995. PMID: 7796813 Free PMC article.
-
Regulation of NFKB1 proteins by the candidate oncoprotein BCL-3: generation of NF-kappaB homodimers from the cytoplasmic pool of p50-p105 and nuclear translocation.EMBO J. 1997 Jun 16;16(12):3609-20. doi: 10.1093/emboj/16.12.3609. EMBO J. 1997. PMID: 9218802 Free PMC article.
-
I kappaB alpha physically interacts with a cytoskeleton-associated protein through its signal response domain.Mol Cell Biol. 1997 Dec;17(12):7375-85. doi: 10.1128/MCB.17.12.7375. Mol Cell Biol. 1997. PMID: 9372968 Free PMC article.
-
Attenuation of apoptosis underlies B lymphocyte stimulator enhancement of humoral immune response.J Exp Med. 2000 Oct 2;192(7):953-64. doi: 10.1084/jem.192.7.953. J Exp Med. 2000. PMID: 11015437 Free PMC article.
-
I(kappa)B(gamma) inhibits DNA binding of NF-kappaB p50 homodimers by interacting with residues that contact DNA.Mol Cell Biol. 1996 Nov;16(11):6477-85. doi: 10.1128/MCB.16.11.6477. Mol Cell Biol. 1996. PMID: 8887676 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
