| First Author | Lee SF | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 47 | Pages | 45013-9 |
| PubMed ID | 12297508 | Mgi Jnum | J:80170 |
| Mgi Id | MGI:2445234 | Doi | 10.1074/jbc.M208164200 |
| Citation | Lee SF, et al. (2002) Mammalian APH-1 Interacts with Presenilin and Nicastrin and Is Required for Intramembrane Proteolysis of Amyloid-beta Precursor Protein and Notch. J Biol Chem 277(47):45013-9 |
| abstractText | Presenilin and nicastrin are essential components of the gamma-secretase complex that is required for the intramembrane proteolysis of an increasing number of membrane proteins including the amyloid-beta precursor protein (APP) and Notch. By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian APH-1 (mAPH-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain. Similar to the loss of presenilin or nicastrin, the inactivation of endogenous mAPH-1 using small interfering RNAs results in the decrease of presenilin levels, accumulation of gamma-secretase substrates (APP carboxyl-terminal fragments), and reduction of gamma-secretase products (amyloid-beta peptides and the intracellular domains of APP and Notch). These data indicate that mAPH-1 is probably a functional component of the gamma-secretase complex required for the intramembrane proteolysis of APP and Notch. |
