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Direct regulation of the Nrarp gene promoter by the Notch signaling pathway
- Source :
-
Biochemical & Biophysical Research Communications . Sep2004, Vol. 322 Issue 2, p526-534. 9p. - Publication Year :
- 2004
-
Abstract
- 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 ∼2 and ∼3kb upstream of the transcription start site each containing a perfect putative binding site for the Notch-dependent transcription factor Su(H). A 4.4kb 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 −3kb 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. [Copyright &y& Elsevier]
- Subjects :
- *CELLS
*PROTEINS
*TRANSCRIPTION factors
*FIRE assay
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 322
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 14189354
- Full Text :
- https://doi.org/10.1016/j.bbrc.2004.07.157