pubmed-article:12771124 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:12771124 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
pubmed-article:12771124 | lifeskim:mentions | umls-concept:C0178555 | lld:lifeskim |
pubmed-article:12771124 | lifeskim:mentions | umls-concept:C1879748 | lld:lifeskim |
pubmed-article:12771124 | lifeskim:mentions | umls-concept:C1706853 | lld:lifeskim |
pubmed-article:12771124 | lifeskim:mentions | umls-concept:C0332120 | lld:lifeskim |
pubmed-article:12771124 | lifeskim:mentions | umls-concept:C0379528 | lld:lifeskim |
pubmed-article:12771124 | pubmed:issue | 4 | lld:pubmed |
pubmed-article:12771124 | pubmed:dateCreated | 2003-5-28 | lld:pubmed |
pubmed-article:12771124 | pubmed:abstractText | The gamma-secretase complex is required for intramembrane cleavage of several integral membrane proteins, including the Notch receptor, where it generates an active signaling fragment. Four putative gamma-secretase components have been identified-presenilin (Psn), nicastrin (Nct), Aph-1, and Pen-2. Here, we use a stepwise coexpression approach to investigate the role of each new component in gamma-secretase assembly and activation. Coexpression of all four proteins leads to high level accumulation of mature Psn and increased proteolysis of Notch. Aph-1 and Nct may form a subcomplex that stabilizes the Psn holoprotein at an early step in gamma-secretase assembly. Subcomplex levels of Aph-1 are down-regulated by stepwise addition of Psn, suggesting that Aph-1 might not enter the mature complex. In contrast, Pen-2 accumulates proportionally with Psn, and is associated with Psn endoproteolysis during gamma-secretase assembly. These results demonstrate that Aph-1 and Pen-2 are essential cofactors for Psn, but that they play different roles in gamma-secretase assembly and activation. | lld:pubmed |
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pubmed-article:12771124 | pubmed:language | eng | lld:pubmed |
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pubmed-article:12771124 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:12771124 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:12771124 | pubmed:month | May | lld:pubmed |
pubmed-article:12771124 | pubmed:issn | 0021-9525 | lld:pubmed |
pubmed-article:12771124 | pubmed:author | pubmed-author:MAIERN R FNR | lld:pubmed |
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pubmed-article:12771124 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:12771124 | pubmed:day | 26 | lld:pubmed |
pubmed-article:12771124 | pubmed:volume | 161 | lld:pubmed |
pubmed-article:12771124 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:12771124 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:12771124 | pubmed:pagination | 685-90 | lld:pubmed |
pubmed-article:12771124 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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pubmed-article:12771124 | pubmed:year | 2003 | lld:pubmed |
pubmed-article:12771124 | pubmed:articleTitle | Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex. | lld:pubmed |
pubmed-article:12771124 | pubmed:affiliation | University of Pennsylvania School of Medicine, Philadelphia 19104, USA. | lld:pubmed |
pubmed-article:12771124 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:12771124 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
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