Gene Set: FUKUSHIMA_TNFSF11_TARGETS

Standard name FUKUSHIMA_TNFSF11_TARGETS
Systematic name M2207
Brief description Genes up-regulated in RAW 264.7 cells (macrophage) upon stimulation with TNFSF11 [GeneID=8600].
Full description or abstract Notch signaling plays a key role in various cell differentiation processes including bone homeostasis. However, the specific involvement of Notch in regulating osteoclastogenesis is still controversial. In the present study, we show that RANKL induces expression of Jagged1 and Notch2 in bone marrow macrophages during osteoclast differentiation. Suppression of Notch signaling by a selective gamma-secretase inhibitor or Notch2 short hairpin RNA suppresses RANKL-induced osteoclastogenesis. In contrast, induction of Notch signaling by Jagged1 or by ectopic expression of intracellular Notch2 enhances NFATc1 promoter activity and expression and promotes osteoclastogenesis. Finally, we found that Notch2 and p65 interact in the nuclei of RANKL-stimulated cells and that both proteins are recruited to the NFATc1 promoter, driving its expression. Taken together, our results show a new molecular cross talk between Notch and NF-kappaB pathways that is relevant in osteoclastogenesis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18710934   Authors: Fukushima H,Nakao A,Okamoto F,Shin M,Kajiya H,Sakano S,Bigas A,Jimi E,Okabe K
Exact source Table 1
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Organism Mus musculus
Contributed by Arthur Liberzon (Broad Institute)
Source platform SEQ_ACCESSION
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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