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

Jagged1 belongs to the DSL family of ligands for Notch receptors that contr ol the proliferation and differentiation of various cell lineages. However, little is known about the transcription factors that regulate its expressi on. Here, we show that Jagged1 is a Rel/ NF-kappa B-responsive gene. Both c -Rel and RelA induced jagged1 gene expression, whereas a mutant defective f or transactivation did not. Importantly,jagged1 transcripts were also upreg ulated by endogenous NF-kappa B activation and this effect was inhibited by a dominant mutant of I kappa B alpha, a physiological inhibitor of NF-kapp a B. 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-cultiva ted T cells and of CD23 transcripts in co-cultivated B cells. Consistent wi th its Rel/NF-kappa B-dependent induction, Jagged1 was found to be highly e xpressed in splenic B cells where c-Rel is expressed constitutively. These results demonstrate that c-Rel can trigger the Notch signaling pathway in n eighboring cells by inducing jagged1 gene expression, and suggest a role fo r Jagged1 in B-cell activation, differentiation or function, These findings also highlight the potential for an interplay between the Notch and NF-kap pa B signaling pathways in the immune system.