Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation.

Developmental cell | Jul 11, 2002

http://www.ncbi.nlm.nih.gov/pubmed/12110170

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.

Pubmed ID: 12110170 RIS Download

Mesh terms: Alzheimer Disease | Amyloid Precursor Protein Secretases | Amyloid beta-Protein Precursor | Animals | Aspartic Acid Endopeptidases | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Cell Membrane | Cells, Cultured | Cloning, Molecular | Drosophila Proteins | Drosophila melanogaster | Endopeptidases | Enhancer Elements, Genetic | Glucagon | Glucagon-Like Peptide 1 | Helminth Proteins | Homeodomain Proteins | Humans | Intracellular Membranes | Membrane Proteins | Molecular Sequence Data | Mutation | Peptide Fragments | Presenilin-1 | Protein Precursors | Receptors, Notch | Sequence Homology, Amino Acid | Sequence Homology, Nucleic Acid | Signal Transduction

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

WormBase (Data, Gene Expression)

GO (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.