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Article: Mutation of conserved aspartates affects maturation of both aspartate mutant and endogenous presenilin 1 and presenilin 2 complexes
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TitleMutation of conserved aspartates affects maturation of both aspartate mutant and endogenous presenilin 1 and presenilin 2 complexes
 
AuthorsYu, G2 3
Chen, F2 3
Nishimura, M2 3
Steiner, H1
Tandon, A2 3
Kawarai, T2 3
Arawaka, S2 3
Supala, A2 3
Song, YQ2 3
Rogaeva, E2 3
Holmes, E2 3
Zhang, DM2 3
Milman, P2 3
Fraser, PE2 3
Haass, C1
St GeorgeHyslop, P3 2
 
Issue Date2000
 
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
CitationJournal Of Biological Chemistry, 2000, v. 275 n. 35, p. 27348-27353 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M002982200
 
AbstractPresenilin (PS1 and PS2) holoproteins are transiently incorporated into low molecular weight (MW) complexes. During subsequent incorporation into a higher MW complex, they undergo endoproteolysis to generate stable N- and C-terminal fragments. Mutation of either of two conserved aspartate residues in transmembrane domains inhibits both presenilin-endoproteolysis and the proteolytic processing of β-amyloid precursor protein and Notch. We show that although PS1/PS2 endoproteolysis is not required for inclusion into the higher MW N- and C-terminal fragment-containing complex, aspartate mutant holoprotein presenilins are not incorporated into the high MW complexes. Aspartate mutant presenilin holoproteins also preclude entry of endogenous wild type PS1/PS2 into the high MW complexes but do not affect the incorporation of wild type holoproteins into lower MW holoprotein complexes. These data suggest that the loss of function effects of the aspartate mutants results in altered PS complex maturation and argue that the functional presenilin moieties are contained in the high molecular weight complexes.
 
ISSN0021-9258
2013 Impact Factor: 4.600
 
DOIhttp://dx.doi.org/10.1074/jbc.M002982200
 
ISI Accession Number IDWOS:000089144800091
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorYu, G
 
dc.contributor.authorChen, F
 
dc.contributor.authorNishimura, M
 
dc.contributor.authorSteiner, H
 
dc.contributor.authorTandon, A
 
dc.contributor.authorKawarai, T
 
dc.contributor.authorArawaka, S
 
dc.contributor.authorSupala, A
 
dc.contributor.authorSong, YQ
 
dc.contributor.authorRogaeva, E
 
dc.contributor.authorHolmes, E
 
dc.contributor.authorZhang, DM
 
dc.contributor.authorMilman, P
 
dc.contributor.authorFraser, PE
 
dc.contributor.authorHaass, C
 
dc.contributor.authorSt GeorgeHyslop, P
 
dc.date.accessioned2011-07-14T07:02:57Z
 
dc.date.available2011-07-14T07:02:57Z
 
dc.date.issued2000
 
dc.description.abstractPresenilin (PS1 and PS2) holoproteins are transiently incorporated into low molecular weight (MW) complexes. During subsequent incorporation into a higher MW complex, they undergo endoproteolysis to generate stable N- and C-terminal fragments. Mutation of either of two conserved aspartate residues in transmembrane domains inhibits both presenilin-endoproteolysis and the proteolytic processing of β-amyloid precursor protein and Notch. We show that although PS1/PS2 endoproteolysis is not required for inclusion into the higher MW N- and C-terminal fragment-containing complex, aspartate mutant holoprotein presenilins are not incorporated into the high MW complexes. Aspartate mutant presenilin holoproteins also preclude entry of endogenous wild type PS1/PS2 into the high MW complexes but do not affect the incorporation of wild type holoproteins into lower MW holoprotein complexes. These data suggest that the loss of function effects of the aspartate mutants results in altered PS complex maturation and argue that the functional presenilin moieties are contained in the high molecular weight complexes.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Biological Chemistry, 2000, v. 275 n. 35, p. 27348-27353 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M002982200
 
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M002982200
 
dc.identifier.epage27353
 
dc.identifier.isiWOS:000089144800091
 
dc.identifier.issn0021-9258
2013 Impact Factor: 4.600
 
dc.identifier.issue35
 
dc.identifier.pmid10856299
 
dc.identifier.scopuseid_2-s2.0-0034282749
 
dc.identifier.spage27348
 
dc.identifier.urihttp://hdl.handle.net/10722/134762
 
dc.identifier.volume275
 
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Biological Chemistry
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAspartic Acid/*genetics
 
dc.subject.meshCell Line
 
dc.subject.meshHumans
 
dc.subject.meshMembrane Proteins/genetics/*physiology
 
dc.subject.meshMutagenesis
 
dc.subject.meshPresenilin-1
 
dc.subject.meshPresenilin-2
 
dc.subject.meshProtein Processing, Post-Translational
 
dc.titleMutation of conserved aspartates affects maturation of both aspartate mutant and endogenous presenilin 1 and presenilin 2 complexes
 
dc.typeArticle
 
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<contributor.author>Tandon, A</contributor.author>
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<contributor.author>Song, YQ</contributor.author>
<contributor.author>Rogaeva, E</contributor.author>
<contributor.author>Holmes, E</contributor.author>
<contributor.author>Zhang, DM</contributor.author>
<contributor.author>Milman, P</contributor.author>
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Author Affiliations
  1. Adolf-Butenandt-Institut
  2. Toronto Western Hospital University of Toronto
  3. University of Toronto