AI Article Synopsis
- - Notch signaling is crucial for development and maintaining balance in multicellular organisms, and when it's off-balance, it can lead to various diseases in humans.
- - The protein RBPJ plays a key role in this process by either activating or repressing gene expression, depending on its interactions with other proteins and DNA.
- - Researchers examined how RBPJ binds to corepressor SHARP and DNA, finding that mutations preventing SHARP binding impaired RBPJ's ability to repress Notch-related gene transcription, enhancing our understanding of RBPJ's repressive function.
Article Abstract
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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352735 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2018.12.097 | DOI Listing |
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