Direct regulation of the Nrarp gene promoter by the Notch signaling pathway.

P Pirot, Leonardus Van Grunsven, Danny Huylebroeck, Jc Marine, Ej Bellefroid

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


Nrarp encodes for an evolutionarily conserved small ankyrin repeat-containing protein that functions as a negative regulator of Notch signaling. Interestingly, increased Nrarp transcription was observed following induction of Notch signaling, suggesting the existence of a negative feedback loop. We show here that both mouse and human promoter regions of Nrarp share two conserved regions located approximately 2 and approximately 3 kb upstream of the transcription start site each containing a perfect putative binding site for the Notch-dependent transcription factor Su(H). A 4.4 kb genomic fragment of the mouse Nrarp locus containing those conserved regions and fused to a luciferase reporter gene showed basal promoter activity in 293T cells and this activity was strongly increased by the intracellular domain of Notch, NICD. NICD-dependent stimulation was attenuated by a dominant negative mutant of Su(H), Su(H)DBM, and was not observed in Su(H)-deficient cells (OT-11). Promoter bashing and gel shift assays revealed that the most distal putative Su(H) binding site located within the -3 kb conserved element plays a crucial role in this induction. Collectively, these results provide definitive support for direct regulation of the Nrarp gene by the Notch pathway.
Original languageEnglish
Pages (from-to)526-534
Number of pages9
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 2004


  • Nrarp


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