Rel/NF-κB can trigger the Notch signaling pathway by inducing the expression of Jagged1, a ligand for Notch receptors

Judy Bash, Wei Xing Zong, Satnam Banga, Amariliz Rivera, Dean W. Ballard, Yacov Ron, Céline Gélinas

Research output: Contribution to journalArticlepeer-review

168 Scopus citations


Jagged1 belongs to the DSL family of ligands for Notch receptors that control the proliferation and differentiation of various cell lineages. However, little is known about the transcription factors that regulate its expression. Here, we show that Jagged1 is a Rel/ NF-κB-responsive gene. Both c-Rel and RelA induced jagged1 gene expression, whereas a mutant defective for transactivation did not. Importantly, jagged1 transcripts were also upregulated by endogenous NF-κB activation and this effect was inhibited by a dominant mutant of IκBα, a physiological inhibitor of NF-κB. Cell surface expression of Jagged1 in c-Rel-expressing cell monolayers led to a functional interaction with lymphocytes expressing the Notch1/TAN-1 receptor. This correlated with the initiation of signaling downstream of Notch, as evidenced by increased levels of HES-1 transcripts in co-cultivated T cells and of CD23 transcripts in co-cultivated B cells. Consistent with its Rel/NF-κB-dependent induction, Jagged1 was found to be highly expressed in splenic B cells where c-Rel is expressed constitutively. These results demonstrate that c-Rel can trigger the Notch signaling pathway in neighboring cells by inducing jagged1 gene expression, and suggest a role for Jagged1 in B-cell activation, differentiation or function. These findings also highlight the potential for an interplay between the Notch and NF-κB signaling pathways in the immune system.

Original languageEnglish (US)
Pages (from-to)2803-2811
Number of pages9
JournalEMBO Journal
Issue number10
StatePublished - May 17 1999

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


  • Jagged 1
  • NF-κB
  • Notch
  • Rel
  • Tan-1


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