aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation
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.
| Errataetall: | |
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| Medienart: |
Artikel |
| Erscheinungsjahr: |
2002 |
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| Erschienen: |
2002 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:3 |
|---|---|
| Enthalten in: |
Developmental cell - 3(2002), 1 vom: 10. Juli, Seite 85-97 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Francis, Ross [VerfasserIn] |
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| Anmerkungen: |
Date Completed 12.08.2002 Date Revised 12.07.2023 published: Print GENBANK: AF512426, AF512427, AF512428 CommentIn: Dev Cell. 2002 Jul;3(1):6-7. - PMID 12110162 Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM11979280X |
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| 100 | 1 | |a Francis, Ross |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation |
| 264 | 1 | |c 2002 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 12.08.2002 | ||
| 500 | |a Date Revised 12.07.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a GENBANK: AF512426, AF512427, AF512428 | ||
| 500 | |a CommentIn: Dev Cell. 2002 Jul;3(1):6-7. - PMID 12110162 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a APH-1 protein, C elegans |2 NLM | |
| 650 | 7 | |a Amyloid beta-Protein Precursor |2 NLM | |
| 650 | 7 | |a Caenorhabditis elegans Proteins |2 NLM | |
| 650 | 7 | |a Drosophila Proteins |2 NLM | |
| 650 | 7 | |a Helminth Proteins |2 NLM | |
| 650 | 7 | |a Homeodomain Proteins |2 NLM | |
| 650 | 7 | |a Lin-12 protein, C elegans |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a N protein, Drosophila |2 NLM | |
| 650 | 7 | |a PEN-2 protein, C elegans |2 NLM | |
| 650 | 7 | |a PSEN1 protein, human |2 NLM | |
| 650 | 7 | |a Peptide Fragments |2 NLM | |
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| 650 | 7 | |a Protein Precursors |2 NLM | |
| 650 | 7 | |a Receptors, Notch |2 NLM | |
| 650 | 7 | |a aph-2 protein, C elegans |2 NLM | |
| 650 | 7 | |a Glucagon-Like Peptide 1 |2 NLM | |
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| 650 | 7 | |a Endopeptidases |2 NLM | |
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| 650 | 7 | |a Aspartic Acid Endopeptidases |2 NLM | |
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| 650 | 7 | |a BACE1 protein, human |2 NLM | |
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| 700 | 1 | |a McGrath, Garth |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jianhuan |e verfasserin |4 aut | |
| 700 | 1 | |a Ruddy, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Sym, Mary |e verfasserin |4 aut | |
| 700 | 1 | |a Apfeld, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Nicoll, Monique |e verfasserin |4 aut | |
| 700 | 1 | |a Maxwell, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Hai, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Ellis, Michael C |e verfasserin |4 aut | |
| 700 | 1 | |a Parks, Annette L |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jinhe |e verfasserin |4 aut | |
| 700 | 1 | |a Gurney, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Myers, Richard L |e verfasserin |4 aut | |
| 700 | 1 | |a Himes, Carol S |e verfasserin |4 aut | |
| 700 | 1 | |a Hiebsch, Ronald |e verfasserin |4 aut | |
| 700 | 1 | |a Ruble, Cara |e verfasserin |4 aut | |
| 700 | 1 | |a Nye, Jeffrey S |e verfasserin |4 aut | |
| 700 | 1 | |a Curtis, Daniel |e verfasserin |4 aut | |
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