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. 1992 Aug;11(8):3003–3009. 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.

H C Liou 1, G P Nolan 1, S Ghosh 1, T Fujita 1, D Baltimore 1
PMCID: PMC556782  PMID: 1639070

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.

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Selected References

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