| First Author | Berechid BE | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 10 | Pages | 8154-65 |
| PubMed ID | 11756438 | Mgi Jnum | J:75093 |
| Mgi Id | MGI:2175939 | Doi | 10.1074/jbc.M108238200 |
| Citation | Berechid BE, et al. (2002) Identification and characterization of presenilin-independent Notch signaling. J Biol Chem 277(10):8154-65 |
| abstractText | Presenilin (PS) proteins control the proteolytic cleavage that precedes nuclear access of the Notch intracellular domain. Here we observe that a partial activation of the HES1 promoter can be detected in PS1/PS2 (PS1/2) double null cells using Notch1 Delta E constructs or following Delta 1 stimulation, despite an apparent abolition of the production and nuclear accumulation of the Notch intracellular domain. PS1/2-independent Notch activation is sensitive to Numblike, a physiological inhibitor of Notch. PS1/2-independent Notch signaling is also inhibited by an active gamma-secretase inhibitor in the low micromolar range and is not inhibited by an inactive analogue, similar to PS-dependent Notch signaling. However, experiments using a Notch1-Gal4-VP16 fusion protein indicate that the PS1/2-independent activity does not release Gal4-VP16 and is therefore unlikely to proceed via an intramembranous cleavage. These data reveal that a novel PS1/2-independent mechanism plays a partial role in Notch signal transduction. |
