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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2005-12-15
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pubmed:abstractText |
APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 activates caspase 9 and thus initiates a cascade of proteolytic events leading to apoptotic destruction of the cell. Cellular phenotypes were measured using a yeast heterologous expression assay in which human Apaf-1 and other proteins necessary to constitute a functional apoptotic pathway were overexpressed. Apaf-1 variants encoded by APAF1 alleles that segregate with major depression in families linked to chromosome 12 shared a common gain-of-function phenotype in both assay systems. In contrast, other Apaf-1 variants showed neutral or loss-of-function phenotypes. The depression-associated alleles thus have a common phenotype that is distinct from that of non-associated variants. This result suggests an etiologic role for enhanced apoptosis in major depression.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1359-4184
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pubmed:author |
pubmed-author:AbkevichVV,
pubmed-author:BeckAA,
pubmed-author:ChenYY,
pubmed-author:DavenportCC,
pubmed-author:DorwinSS,
pubmed-author:EganD ADA,
pubmed-author:GopalakrishnanMM,
pubmed-author:GubbinsEE,
pubmed-author:HahnAA,
pubmed-author:HalbertD NDN,
pubmed-author:HarlanJJ,
pubmed-author:HolzmanT FTF,
pubmed-author:JohnsonR WRW,
pubmed-author:LIENR MRM,
pubmed-author:LafontM JMJ,
pubmed-author:LakeMM,
pubmed-author:MetzgerPP,
pubmed-author:MuellerRR,
pubmed-author:NeffC DCD,
pubmed-author:OlsenTT,
pubmed-author:PotterJJ,
pubmed-author:SHURS GSG,
pubmed-author:SeverinJJ,
pubmed-author:ShattuckDD,
pubmed-author:SkolnickM HMH,
pubmed-author:SpeakB MBM,
pubmed-author:SullivanJ PJP,
pubmed-author:VoelpKK,
pubmed-author:WalterKK
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
76-85
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16231040-Alleles,
pubmed-meshheading:16231040-Apoptosis,
pubmed-meshheading:16231040-Apoptotic Protease-Activating Factor 1,
pubmed-meshheading:16231040-Depressive Disorder, Major,
pubmed-meshheading:16231040-Genetic Predisposition to Disease,
pubmed-meshheading:16231040-Humans,
pubmed-meshheading:16231040-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16231040-Phenotype,
pubmed-meshheading:16231040-Polymorphism, Genetic,
pubmed-meshheading:16231040-Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
Variants in Apaf-1 segregating with major depression promote apoptosome function.
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pubmed:affiliation |
Advanced Technologies, Abbott Laboratories, 100 Abbott Park Road R424/AP10, Abbott Park, IL 60064, USA.
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pubmed:publicationType |
Journal Article
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