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

By Jun Li, G. W. Peet, D. Balzarano, Xiang Li, P. Massa, R. Barton, K. Marcu. Journal of Biological Chemistry, 2001

141 citations recorded by the source corpus.

The IκB kinase (IKK) signaling complex is responsible for activating NF-κB-dependent gene expression programs. Even though NF-κB-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 cellsversus 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, andCD36) and five repressed (CCR2,VpreB, λ5, SLPI, andCMAP/Cystatin7) genes, respectively, were bona fide NF-κB targets by virtue of their response to a transdominant IκBαSR (super repressor). MyD118 andISG15, 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.

Subfields: Cancer Research, Immunology

View Paper: https://www.semanticscholar.org/paper/fa213c1e10430c020479759539275e3997ec11ac