| First Author | Jung C | Year | 2013 |
| Journal | Biochim Biophys Acta | Volume | 1833 |
| Issue | 5 | Pages | 1180-9 |
| PubMed ID | 23396200 | Mgi Jnum | J:199032 |
| Mgi Id | MGI:5500130 | Doi | 10.1016/j.bbamcr.2013.01.032 |
| Citation | Jung C, et al. (2013) RNA helicase Ddx5 and the noncoding RNA SRA act as coactivators in the Notch signaling pathway. Biochim Biophys Acta 1833(5):1180-9 |
| abstractText | Notch signaling plays a pivotal role in embryonic and postnatal development. Upon binding of a Notch ligand, proteolytic cleavage events liberate the Notch-intracellular domain (NICD) that migrates into the nucleus. In order to activate target genes, NICD associates with the transcription factor RBP-J (also known as CSL), Mastermind and the acetyltransferase p300. Here, we identify the DEAD-box RNA helicase Ddx5 as a novel component of the RBP-J/NICD complex utilizing a biotinylation-tagging approach followed by mass-spectrometry. Biochemical assays confirm a direct interaction of Ddx5 with RBP-J. We show that Ddx5 localizes at RBP-J binding sites within the Notch target genes preTCRalpha, Hes1 and CD25 in a Notch-dependent manner. Moreover, knockdown of Ddx5 also downregulates a subset of Notch target genes in a murine pre T-cell model. Interestingly, also knockdown/overexpression of the RNA coactivator SRA, a cofactor of Ddx5, downregulates Hes1 and preTCRalpha. Using Chromatin-IP, we show that this effect is accompanied with a loss of p300 occupancy at Notch target genes and decreased histone acetylation. Together, our data demonstrate that Ddx5 and SRA function as coactivators of Notch signaling. |
