aph-1 and pen-2 Are Required for Notch Pathway Signaling, γ-Secretase Cleavage of βAPP, and Presenilin Protein Accumulation
| Autor: | Annette L. Parks, Jeffrey S. Nye, Daniel Tim Curtis, Carol S. Himes, Ross Francis, Bing Hai, Jianhuan Zhang, David A. Ruddy, Michael C. Ellis, Richard L. Myers, Ronald Hiebsch, Cara L. Ruble, Javier Apfeld, Jinhe Li, Mark E. Gurney, Mary Sym, Mark E. Maxwell, Garth Joseph Mcgrath, Wei Xu, Monique Nicoll |
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| Rok vydání: | 2002 |
| Předmět: |
Molecular Sequence Data
Nicastrin Notch signaling pathway Biology General Biochemistry Genetics and Molecular Biology Presenilin Amyloid beta-Protein Precursor Alzheimer Disease Glucagon-Like Peptide 1 PEN-2 Sequence Homology Nucleic Acid Endopeptidases mental disorders Presenilin-1 Animals Aspartic Acid Endopeptidases Drosophila Proteins Humans Cloning Molecular Protein Precursors APH-1 Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Cells Cultured Homeodomain Proteins Receptors Notch Sequence Homology Amino Acid Cell Membrane Membrane Proteins Helminth Proteins Intracellular Membranes Cell Biology Glucagon Molecular biology Peptide Fragments Gamma-secretase complex Drosophila melanogaster Enhancer Elements Genetic Notch proteins Mutation biology.protein Amyloid Precursor Protein Secretases Amyloid precursor protein secretase Signal Transduction Developmental Biology |
| Zdroj: | Developmental Cell. 3(1):85-97 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/s1534-5807(02)00189-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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