TY - JOUR
T1 - Novel NEMO/IκB Kinase and NF-κB Target Genes at the Pre-B to Immature B Cell Transition
AU - Li, Jun
AU - Peet, Gregory W.
AU - Balzarano, Darlene
AU - Li, Xiang
AU - Massa, Paul
AU - Barton, Randall W.
AU - Marcu, Kenneth B.
PY - 2001/1/25
Y1 - 2001/1/25
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M100846200
DO - 10.1074/jbc.M100846200
M3 - Article
C2 - 11279141
AN - SCOPUS:0035947608
VL - 276
SP - 18579
EP - 18590
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 21
ER -