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Genetic analysis of NF-κB/Rel transcription factors defines functional specificities

Hoffmann, Alexander and Leung, Thomas H. and Baltimore, David (2003) Genetic analysis of NF-κB/Rel transcription factors defines functional specificities. EMBO Journal, 22 (20). pp. 5530-5539. ISSN 1460-2075. PMCID PMC213788. doi:10.1093/emboj/cdg534.

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The NF‐κB transcription factors consist of dimeric proteins of the Rel homology family. They activate many promoters containing highly divergent κB‐site sequences. We have generated cell lines lacking individual and multiple NF‐κB proteins and used them to establish interactions between components of the NF‐κB–IκB signaling system. Functional compensation within the family of dimers was evident in knockout cell lines. Analysis of transiently transfected genes gave an impression of promiscuity that was not borne out by analysis of endogenous genes. Using TNFα as an inducer, a panel of endogenous genes showed a wide range of subunit specificities as well as highly variable kinetics of induction. Comparing the function and subunit specificity of genes with the sequence of the κB DNA‐binding site we found little correlation, indicating that NF‐κB family member specificity for endogenous promoters is not solely encoded by the κB site sequence itself.

Item Type:Article
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URLURL TypeDescription CentralArticle
Baltimore, David0000-0001-8723-8190
Additional Information:© 2003 European Molecular Biology Organization. Received July 14, 2003; revised August 22, 2003; accepted August 25, 2003. A.H. thanks A.Beg, W.C.Sha, B.H.Horwitz, S.Gerondakis, R.Ryseck and R.Bravo for knockout mice, L.Anonueovo, B.Kennedy and S.Pease for their maintenance, S.Tronick for antibodies, and G.Ghosh and T.Huxford for critical reading of the manuscript. T.H.L. is an ARCS Foundation fellow and part of the UCLA/Caltech Medical Scientist Training Program.
Funding AgencyGrant Number
UCLA/Caltech Medical Scientist Training ProgramUNSPECIFIED
Subject Keywords:compensation/NF‐κB/Rel/specificity/transcription
Issue or Number:20
PubMed Central ID:PMC213788
Record Number:CaltechAUTHORS:20200417-142718187
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Official Citation:Hoffmann, A., Leung, T.H. and Baltimore, D. (2003), Genetic analysis of NF‐κB/Rel transcription factors defines functional specificities. The EMBO Journal, 22: 5530-5539. doi:10.1093/emboj/cdg534
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102635
Deposited By: George Porter
Deposited On:20 Apr 2020 14:15
Last Modified:16 Nov 2021 18:14

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