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PMID: 15470505 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The EMBO journal ·Vol. 23 ·No. 21 ·2004-10-27 ·Pages 4202-10

Bonizzi G, Bebien M, Otero DC, Johnson-Vroom KE, Cao Y, Vu D, Jegga AG, Aronow BJ, Ghosh G, Rickert RC, Karin M

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Adoptive Transfer Animals Base Sequence Binding Sites Bone Marrow Transplantation Cells, Cultured Chemokines/genetics,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,metabolism Protein Structure, Quaternary Proto-Oncogene Proteins/metabolism Receptors, Tumor Necrosis Factor/genetics,metabolism Signal Transduction/physiology Stromal Cells/cytology,physiology Trans-Activators/metabolism Transcription Factor RelB Transcription Factors/metabolism
Chemicals
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
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Bonizzi Giuseppina
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.
Bebien Magali
Otero Dennis C
Johnson-Vroom Kirsten E
Cao Yixue
Vu Don
Jegga Anil G
Aronow Bruce J
Ghosh Gourisankar
Rickert Robert C
Karin Michael
References (37)
37 references, click to expand
  1. IKKalpha provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development.
    Cell. 2001 Dec 14;107(6):763-75 PMID: 11747812
  2. IkappaB kinase alpha is essential for mature B cell development and function.
    J Exp Med. 2001 Feb 19;193(4):417-26 PMID: 11181694
  3. Missing pieces in the NF-kappaB puzzle.
    Cell. 2002 Apr;109 Suppl:S81-96 PMID: 11983155
  4. Visualization of lymphotoxin-beta and lymphotoxin-beta receptor expression in mouse embryos.
    J Immunol. 2002 May 15;168(10):5079-87 PMID: 11994460
  5. CXCR5-transduced bone marrow-derived dendritic cells traffic to B cell zones of lymph nodes and modify antigen-specific immune responses.
    J Immunol. 2002 May 15;168(10):5096-102 PMID: 11994462
  6. Dynamic changes in histone H3 Lys 9 methylation occurring at tightly regulated inducible inflammatory genes.
    Genes Dev. 2002 Sep 1;16(17):2219-24 PMID: 12208844
  7. Detection and visualization of compositionally similar cis-regulatory element clusters in orthologous and coordinately controlled genes.
    Genome Res. 2002 Sep;12(9):1408-17 PMID: 12213778
  8. BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells.
    Nat Immunol. 2002 Oct;3(10):958-65 PMID: 12352969
  9. A chemokine-driven positive feedback loop organizes lymphoid follicles.
    Nature. 2000 Jul 20;406(6793):309-14 PMID: 10917533
  10. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
    Annu Rev Immunol. 2000;18:621-63 PMID: 10837071
  11. Chemokines in lymphopoiesis and lymphoid organ development.
    Curr Opin Immunol. 2001 Apr;13(2):172-9 PMID: 11228410
  12. NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100.
    Mol Cell. 2001 Feb;7(2):401-9 PMID: 11239468
  13. Two waves of nuclear factor kappaB recruitment to target promoters.
    J Exp Med. 2001 Jun 18;193(12):1351-9 PMID: 11413190
  14. Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-kappa B in leukocyte recruitment.
    J Immunol. 2001 Aug 1;167(3):1592-600 PMID: 11466381
  15. Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines.
    J Immunol. 2001 Aug 15;167(4):1909-19 PMID: 11489970
  16. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway.
    Science. 2001 Aug 24;293(5534):1495-9 PMID: 11520989
  17. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2.
    Immunity. 2002 Oct;17(4):515-24 PMID: 12387744
  18. The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways.
    Immunity. 2002 Oct;17(4):525-35 PMID: 12387745
  19. Two pathways to NF-kappaB.
    Mol Cell. 2002 Oct;10(4):693-5 PMID: 12419209
  20. RelB is required for Peyer's patch development: differential regulation of p52-RelB by lymphotoxin and TNF.
    EMBO J. 2003 Jan 2;22(1):121-30 PMID: 12505990
  21. The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion.
    Nat Med. 2003 May;9(5):575-81 PMID: 12692538
  22. Signal transduction: A regulator branches out.
    Nature. 2003 Jun 5;423(6940):596-7 PMID: 12789323
  23. Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression.
    Nature. 2003 Jun 5;423(6940):655-9 PMID: 12789342
  24. A nucleosomal function for IkappaB kinase-alpha in NF-kappaB-dependent gene expression.
    Nature. 2003 Jun 5;423(6940):659-63 PMID: 12789343
  25. Lymphoid organ development and cell migration.
    Immunol Rev. 2003 Oct;195:5-14 PMID: 12969306
  26. Structure of NF-kappa B p50 homodimer bound to a kappa B site.
    Nature. 1995 Jan 26;373(6512):303-10 PMID: 7530332
  27. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.
    Annu Rev Immunol. 1998;16:225-60 PMID: 9597130
  28. Enhancement of terminal B lymphocyte differentiation in vitro by fibroblast-like stromal cells from human spleen.
    Eur J Immunol. 1998 Dec;28(12):3940-8 PMID: 9862330
  29. Chemokines: signal lamps for trafficking of T and B cells for development and effector function.
    J Leukoc Biol. 1999 Jan;65(1):6-15 PMID: 9886241
  30. Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity.
    Mol Cell Biol. 1999 Mar;19(3):1950-60 PMID: 10022882
  31. Severe liver degeneration in mice lacking the IkappaB kinase 2 gene.
    Science. 1999 Apr 9;284(5412):321-5 PMID: 10195897
  32. Development and maturation of secondary lymphoid tissues.
    Annu Rev Immunol. 1999;17:399-433 PMID: 10358764
  33. Construction, expression, purification and functional analysis of recombinant NFkappaB p50/p65 heterodimer.
    Protein Eng. 1999 May;12(5):423-8 PMID: 10360983
  34. RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts.
    Mol Cell Biol. 1999 Nov;19(11):7688-96 PMID: 10523657
  35. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.
    Cell. 1999 Oct 1;99(1):23-33 PMID: 10520991
  36. Distinct activities of p52/NF-kappa B required for proper secondary lymphoid organ microarchitecture: functions enhanced by Bcl-3.
    J Immunol. 1999 Dec 15;163(12):6581-8 PMID: 10586052
  37. The NF-kappa B activation pathway: a paradigm in information transfer from membrane to nucleus.
    Sci STKE. 1999 Oct 26;1999(5):RE1 PMID: 11865184
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600391
Published
2004-10-27
Epub
2004-00-07
Pages
4202-10
Language
English
Region
England
NLM ID
8208664
PMCID
PMC524385
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600391 PMC Full Text View journal details
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