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PMID: 14532125 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 22 ·No. 20 ·2003-10-15 ·Pages 5530-9

Hoffmann A, Leung TH, Baltimore D

Abstract

The NF-kappaB transcription factors consist of dimeric proteins of the Rel homology family. They activate many promoters containing highly divergent kappaB-site sequences. We have generated cell lines lacking individual and multiple NF-kappaB proteins and used them to establish interactions between components of the NF-kappaB-IkappaB 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 TNFalpha 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 kappaB DNA-binding site we found little correlation, indicating that NF-kappaB family member specificity for endogenous promoters is not solely encoded by the kappaB site sequence itself.

MeSH Terms
3T3 Cells Animals Base Sequence Dimerization Kinetics Mice NF-kappa B/genetics,metabolism Oncogene Proteins v-rel/genetics,metabolism Promoter Regions, Genetic Protein Subunits Recombinant Proteins/metabolism Ribonucleases Transfection
Chemicals
NF-kappa B Oncogene Proteins v-rel Protein Subunits Recombinant Proteins Ribonucleases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hoffmann Alexander
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Leung Thomas H
Baltimore David
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg534
Published
2003-10-15
Pages
5530-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC213788
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg534 PMC Full Text View journal details
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