Novel NEMO/IκB Kinase and NF-κB Target Genes at the Pre-B to Immature B Cell Transition

Jun Li, Gregory W. Peet, Darlene Balzarano, Xiang Li, Paul Massa, Randall W. Barton, Kenneth B. Marcu

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

The IκB kinase (IKK) signaling complex is responsible for activating NF-κB-dependent gene expression programs. Even though NF-κ B-responsive genes are known to orchestrate stress-like responses, critical gaps in our knowledge remain about the global effects of NF-κB activation on cellular physiology. DNA microarrays were used to compare gene expression programs in a model system of 70Z/3 murine pre-B cells versus their IKK signaling-defective 1.3E2 variant with lipopolysaccharide (LPS), interleukin-1 (IL-1), or a combination of LPS + phorbol 12-myristate 13-acetate under brief (2 h) or long term (12 h) stimulation. 70Z/3.1.3E2 cells lack expression of NEMO/IKKγ/IKKAP-1/FIP-3, an essential positive effector of the IKK complex. Some stimulated hits were known NF-κB target genes, but remarkably, the vast majority of the up-modulated genes and an unexpected class of repressed genes were all novel targets of this signaling pathway, encoding transcription factors, receptors, extracellular ligands, and intracellular signaling factors. Thirteen stimulated (B-ATF, Pim-2, MyD118, Pea-15/MAT1, CD82, CD40L, Wnt10a, Notch 1, R-ras, Rgs-16, PAC-1, ISG15, and CD36) and five repressed (CCR2, VpreB, λ5, SLPI, and CMAP/Cystatin7) genes, respectively, were bona fide NF-κB targets by virtue of their response to a transdominant IκBαSR (super repressor). MyD118 and ISG15, although directly induced by LPS stimulation, were unaffected by IL-1, revealing the existence of direct NF-κB target genes, which are not co-induced by the LPS and IL-1 Toll-like receptors.

Original languageEnglish
Pages (from-to)18579-18590
Number of pages12
JournalJournal of Biological Chemistry
Volume276
Issue number21
DOIs
Publication statusPublished - Jan 25 2001

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B-Lymphoid Precursor Cells
Phosphotransferases
Genes
Cells
Lipopolysaccharides
Interleukin-1
Gene expression
Gene Expression
CD40 Ligand
Toll-Like Receptors
Peas
Physiology
Microarrays
Oligonucleotide Array Sequence Analysis
Acetates
Transcription Factors
Chemical activation
Ligands
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Novel NEMO/IκB Kinase and NF-κB Target Genes at the Pre-B to Immature B Cell Transition. / Li, Jun; Peet, Gregory W.; Balzarano, Darlene; Li, Xiang; Massa, Paul; Barton, Randall W.; Marcu, Kenneth B.

In: Journal of Biological Chemistry, Vol. 276, No. 21, 25.01.2001, p. 18579-18590.

Research output: Contribution to journalArticle

Li, Jun ; Peet, Gregory W. ; Balzarano, Darlene ; Li, Xiang ; Massa, Paul ; Barton, Randall W. ; Marcu, Kenneth B. / Novel NEMO/IκB Kinase and NF-κB Target Genes at the Pre-B to Immature B Cell Transition. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 21. pp. 18579-18590.
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