AI Article Synopsis
- - Notch signaling is activated when the Notch receptor is cleaved after interacting with its ligands, and Jagged-1 can also be cleaved to release a fragment called Jagged-1 intracellular domain (JICD).
- - The study shows that JICD inhibits Notch1 signaling by destabilizing the Notch1 intracellular domain (Notch1-IC), thereby preventing the formation of a key signaling complex.
- - JICD promotes the degradation of Notch1-IC through the Fbw7 proteasomal pathway, acting as a negative regulator of Notch1 signaling.
Article Abstract
Notch signaling involves the proteolytic cleavage of the transmembrane Notch receptor after binding to its transmembrane ligands. Jagged-1 also undergoes proteolytic cleavage by gamma-secretase and releases an intracellular fragment. In this study, we have demonstrated that the Jagged-1 intracellular domain (JICD) inhibits Notch1 signaling via a reduction in the protein stability of the Notch1 intracellular domain (Notch1-IC). The formation of the Notch1-IC-RBP-Jk-Mastermind complex is prevented in the presence of JICD, via a physical interaction. Furthermore, JICD accelerates the protein degradation of Notch1-IC via Fbw7-dependent proteasomal pathway. These results indicate that JICD functions as a negative regulator in Notch1 signaling via the promotion of Notch1-IC degradation.
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| http://dx.doi.org/10.1016/j.yexcr.2011.07.014 | DOI Listing |
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