Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers

Giuseppina Bonizzi; Magali Bebien; Dennis C Otero; Kirsten E Johnson-Vroom; Yixue Cao; Don Vu; Anil G Jegga; Bruce J Aronow; Gourisankar Ghosh; Robert C Rickert; Michael Karin

doi:10.1038/sj.emboj.7600391

Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers

EMBO J. 2004 Oct 27;23(21):4202-10. doi: 10.1038/sj.emboj.7600391. Epub 2004 Oct 7.

Authors

Giuseppina Bonizzi¹, Magali Bebien, Dennis C Otero, Kirsten E Johnson-Vroom, Yixue Cao, Don Vu, Anil G Jegga, Bruce J Aronow, Gourisankar Ghosh, Robert C Rickert, Michael Karin

Affiliation

¹ Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.

Abstract

IkappaB Kinase (IKK)alpha is required for activation of an alternative NF-kappaB signaling pathway based on processing of the NF-kappaB2/p100 precursor protein, which associates with RelB in the cytoplasm. This pathway, which activates RelB:p52 dimers, is required for induction of several chemokine genes needed for organization of secondary lymphoid organs. We investigated the basis for the IKKalpha dependence of the induction of these genes in response to engagement of the lymphotoxin beta receptor (LTbetaR). Using chromatin immunoprecipitation, we found that the promoters of organogenic chemokine genes are recognized by RelB:p52 dimers and not by RelA:p50 dimers, the ubiquitous target for the classical NF-kappaB signaling pathway. We identified in the IKKalpha-dependent promoters a novel type of NF-kappaB-binding site that is preferentially recognized by RelB:p52 dimers. This site links induction of organogenic chemokines and other important regulatory molecules to activation of the alternative pathway.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adaptor Proteins, Signal Transducing
Adoptive Transfer
Animals
Base Sequence
Binding Sites
Bone Marrow Transplantation
Cells, Cultured
Chemokines / genetics
Chemokines / metabolism
Dimerization
Gene Expression Regulation*
I-kappa B Kinase
Lymphotoxin beta Receptor
Mice
Mice, Knockout
Molecular Sequence Data
NF-kappa B / metabolism
Promoter Regions, Genetic
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Protein Structure, Quaternary*
Proto-Oncogene Proteins / metabolism*
Receptors, Tumor Necrosis Factor / genetics
Receptors, Tumor Necrosis Factor / metabolism
Signal Transduction / physiology
Stromal Cells / cytology
Stromal Cells / physiology
Trans-Activators / metabolism*
Transcription Factor RelB
Transcription Factors / metabolism*

Substances

Adaptor Proteins, Signal Transducing
Chemokines
Ltbr protein, mouse
Lymphotoxin beta Receptor
NF-kappa B
Proto-Oncogene Proteins
Psip1 protein, mouse
Receptors, Tumor Necrosis Factor
Relb protein, mouse
Trans-Activators
Transcription Factors
Transcription Factor RelB
Protein Serine-Threonine Kinases
Chuk protein, mouse
I-kappa B Kinase
Ikbkb protein, mouse
Ikbke protein, mouse