aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation.
Dev Cell
; 3(1): 85-97, 2002 Jul.
Article
em En
| MEDLINE
| ID: mdl-12110170
ABSTRACT
Presenilins are components of the gamma-secretase protein complex that mediates intramembranous cleavage of betaAPP and Notch proteins. A C. elegans genetic screen revealed two genes, aph-1 and pen-2, encoding multipass transmembrane proteins, that interact strongly with sel-12/presenilin and aph-2/nicastrin. Human aph-1 and pen-2 partially rescue the C. elegans mutant phenotypes, demonstrating conserved functions. The human genes must be provided together to rescue the mutant phenotypes, and the inclusion of presenilin-1 improves rescue, suggesting that they interact closely with each other and with presenilin. RNAi-mediated inactivation of aph-1, pen-2, or nicastrin in cultured Drosophila cells reduces gamma-secretase cleavage of betaAPP and Notch substrates and reduces the levels of processed presenilin. aph-1 and pen-2, like nicastrin, are required for the activity and accumulation of gamma-secretase.
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Base de dados:
MEDLINE
Assunto principal:
Endopeptidases
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Membrana Celular
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Precursor de Proteína beta-Amiloide
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Proteínas de Homeodomínio
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Proteínas de Caenorhabditis elegans
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Proteínas de Membrana
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article