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NF-κB p50 precursor, p105, contains an internal IκB-like inhibitor that preferentially inhibits p50

Liou, Hsiou-Chi and Nolan, Garry P. and Ghosh, Sankar and Fujita, Takashi and Baltimore, David (1992) NF-κB p50 precursor, p105, contains an internal IκB-like inhibitor that preferentially inhibits p50. EMBO Journal, 11 (8). pp. 3003-3009. ISSN 0261-4189. PMCID PMC556782. https://resolver.caltech.edu/CaltechAUTHORS:20200514-151613822

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Abstract

The p50 subunit of NF‐κB 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 IκB 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‐κB 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 κB motif but minimally affects the binding of p65 homodimers and NF‐κB. By contrast, MAD‐3 inhibits the binding of p65 and NF‐κB 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/j.1460-2075.1992.tb05370.xDOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC556782PubMed CentralArticle
ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 1992 European Molecular Biology Organization. Received on February 18, 1992; revised on April 28, 1992. The authors greatly appreciate Drs L.H. Glimcher, B.Mayer, E. Spanopolous, K. Saksela, Z.-S.Ye and M.Scott for reviewing the manuscript. Special acknowledgement goes to Dr E. Spanopoulou for providing various B cell extracts for immunologic analysis. We also thank Drs Inoue and I. Verma for communicating results to us before publication. The research was supported by fellowships from Cancer Research Institute (H.-C.L.), National Institute of Health (G.P.N.), Irvington Institute for Medical Research (S.G.), Human Frontier Science Program (T.F.) and the NIH grant GM39458-04 (D.B.).
Funders:
Funding AgencyGrant Number
Cancer Research InstituteUNSPECIFIED
NIHGM39458-04
Irvington Institute for Medical ResearchUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Subject Keywords:ankyrin repeats; IκB; NF-κB; p105
Issue or Number:8
PubMed Central ID:PMC556782
Record Number:CaltechAUTHORS:20200514-151613822
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200514-151613822
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103213
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:14 May 2020 22:26
Last Modified:14 May 2020 22:26

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