Title : Deciphering the
Fringe-Mediated Notch Code: Identification of Activating and Inhibiting Sites Allowing Discrimination between Ligands
Abstract :
- Fringe proteins are β3-N-acetylglucosaminyltransferases that modulate Notch activity by modifying O-fucose residues on epidermal growth factor-like (EGF) repeats of Notch
- Mammals have three Fringes: Lunatic, Manic, and Radical
- While Lunatic and Manic Fringe inhibit Notch1 activation from Jagged1 and enhance activation from Delta-like 1 , Radical Fringe enhances signaling from both
- We used a mass spectrometry approach to determine whether the variable effects of Fringes on Notch1 result from generation of unique glycosylation patterns on Notch1
- We found that Lunatic and Manic Fringe modified similar sites on Notch1 , while Radical Fringe modified a subset
- Fringe modifications at EGF8 and EGF12 enhanced Notch1 binding to and activation from Delta-like 1 , while modifications at EGF6 and EGF36 (added by Manic and Lunatic but not Radical) inhibited Notch1 activation from Jagged1
- Combined, these results suggest that Fringe modifications "mark" different regions in the Notch1 extracellular domain for activation or inhibition
Output (sent_index, trigger,
protein,
sugar,
site):
- 1. Notch, , Notch, epidermal growth factor-like (EGF) repeats, -
Output(Part-Of) (sent_index,
protein,
site):
- 5. Notch1, sites
- 7. -, domain
- 7. Notch1, domain
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):