The NF-kappa B p50 precursor, p105, contains an internal I kappa B-like inhibitor that preferentially inhibits p50
- PMID: 1639070
- PMCID: PMC556782
- DOI: 10.1002/j.1460-2075.1992.tb05370.x
The NF-kappa B p50 precursor, p105, contains an internal I kappa B-like inhibitor that preferentially inhibits p50
Abstract
The p50 subunit of NF-kappa B is apparently synthesized as a precursor molecule of 105 kDa (p105); subsequent processing releases the amino-terminal p50 polypeptide with rel homology, DNA binding activity and transcriptional activation potential. The carboxy-terminal region of p105 contains seven copies of an ankyrin-related sequence previously found in several genes involved in differentiation and cell cycle control. Two proteins with I kappa B activity, MAD-3 and pp40, have been cloned and found to contain five obvious ankyrin repeats that align with those in the carboxy-terminus of p105. Both proteins target their inhibitory activity to the p65 subunit of NF-kappa B and to c-rel. Here we show that the bacterially expressed and purified carboxy-terminal region (CTR) of p105 abolishes the binding of p50 homodimers to a kappa B motif but minimally affects the binding of p65 homodimers and NF-kappa B. By contrast, MAD-3 inhibits the binding of p65 and NF-kappa B but not p50. Both the CTR and MAD-3 interact with their respective targets through physical association both in vitro and in vivo. The CTR can be expressed as an independent entity and thus may play two roles, as a cis inhibitor built into the p105 molecule and as a trans regulator of p50.
Similar articles
-
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
-
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 precursor of NF-kappa B p50 has I kappa B-like functions.Cell. 1992 Oct 16;71(2):243-53. doi: 10.1016/0092-8674(92)90353-e. Cell. 1992. PMID: 1423592
-
The NF-ĸB p50 subunit generated by KPC1-mediated ubiquitination and limited proteasomal processing, suppresses tumor growth.Cancer Cell Int. 2023 Apr 13;23(1):67. doi: 10.1186/s12935-023-02919-5. Cancer Cell Int. 2023. PMID: 37055826 Free PMC article. Review.
Cited by
-
X-ray Crystallographic Study of Preferred Spacing by the NF-κB p50 Homodimer on κB DNA.Biomolecules. 2023 Aug 26;13(9):1310. doi: 10.3390/biom13091310. Biomolecules. 2023. PMID: 37759710 Free PMC article.
-
Origin of the Functional Distinctiveness of NF-κB/p52.Front Cell Dev Biol. 2021 Nov 23;9:764164. doi: 10.3389/fcell.2021.764164. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 34888310 Free PMC article. Review.
-
Transformation of avian fibroblasts overexpressing the c-rel proto-oncogene and a variant of c-rel lacking 40 C-terminal amino acids.J Virol. 1994 Apr;68(4):2073-83. doi: 10.1128/JVI.68.4.2073-2083.1994. J Virol. 1994. PMID: 8138992 Free PMC article.
-
Proteolytic degradation of MAD3 (I kappa B alpha) and enhanced processing of the NF-kappa B precursor p105 are obligatory steps in the activation of NF-kappa B.Nucleic Acids Res. 1993 Nov 11;21(22):5059-66. doi: 10.1093/nar/21.22.5059. Nucleic Acids Res. 1993. PMID: 8255759 Free PMC article.
-
The Ubiquitination of NF-κB Subunits in the Control of Transcription.Cells. 2016 May 12;5(2):23. doi: 10.3390/cells5020023. Cells. 2016. PMID: 27187478 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
