| First Author | Yuan Z | Year | 2019 |
| Journal | Cell Rep | Volume | 26 |
| Issue | 4 | Pages | 845-854.e6 |
| PubMed ID | 30673607 | Mgi Jnum | J:288403 |
| Mgi Id | MGI:6432067 | Doi | 10.1016/j.celrep.2018.12.097 |
| Citation | Yuan Z, et al. (2019) Structural and Functional Studies of the RBPJ-SHARP Complex Reveal a Conserved Corepressor Binding Site. Cell Rep 26(4):845-854.e6 |
| abstractText | Notch is a conserved signaling pathway that is essential for metazoan development and homeostasis; dysregulated signaling underlies the pathophysiology of numerous human diseases. Receptor-ligand interactions result in gene expression changes, which are regulated by the transcription factor RBPJ. RBPJ forms a complex with the intracellular domain of the Notch receptor and the coactivator Mastermind to activate transcription, but it can also function as a repressor by interacting with corepressor proteins. Here, we determine the structure of RBPJ bound to the corepressor SHARP and DNA, revealing its mode of binding to RBPJ. We tested structure-based mutants in biophysical and biochemical-cellular assays to characterize the role of RBPJ as a repressor, clearly demonstrating that RBPJ mutants deficient for SHARP binding are incapable of repressing transcription of genes responsive to Notch signaling in cells. Altogether, our structure-function studies provide significant insights into the repressor function of RBPJ. |
