schliessen

Filtern

 

Bibliotheken

TMP21 is a presenilin complex component that modulates γ-secretase but not ε-secretase activity

The presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref. 5) form a series of high-molecular-mass, membrane-bound protein complexes that are necessary for gamma-secretase and epsilon-secretase cleavage of selected type 1 transmembrane proteins,... Full description

Journal Title: Nature 2006, Vol.440 (7088), p.1208-1212
Main Author: FUSHENG CHEN
Other Authors: HASEGAWA, Hiroshi , WAKUTANI, Yosuke , PARDOSSI-PIQUARD, Raphaëlle , XUEYING RUAN , TANDON, Anurag , CHECLER, Frédéric , MARAMBAUD, Philippe , HANSEN, Kirk , WESTAWAY, David , ST GEORGE-HYSLOP, Peter , FRASER, Paul , SCHMITT-ULMS, Gerold , KAWARAI, Toshitaka , BOHM, Christopher , KATAYAMA, Taiichi , YONGJUN GU , SANJO, Nobuo , GLISTA, Michael , ROGAEVA, Ekaterina
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: London: Nature Publishing
ID: ISSN: 0028-0836
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_proquest_miscellaneous_67906547
title: TMP21 is a presenilin complex component that modulates γ-secretase but not ε-secretase activity
format: Article
creator:
  • FUSHENG CHEN
  • HASEGAWA, Hiroshi
  • WAKUTANI, Yosuke
  • PARDOSSI-PIQUARD, Raphaëlle
  • XUEYING RUAN
  • TANDON, Anurag
  • CHECLER, Frédéric
  • MARAMBAUD, Philippe
  • HANSEN, Kirk
  • WESTAWAY, David
  • ST GEORGE-HYSLOP, Peter
  • FRASER, Paul
  • SCHMITT-ULMS, Gerold
  • KAWARAI, Toshitaka
  • BOHM, Christopher
  • KATAYAMA, Taiichi
  • YONGJUN GU
  • SANJO, Nobuo
  • GLISTA, Michael
  • ROGAEVA, Ekaterina
subjects:
  • Amyloid beta-Peptides - biosynthesis
  • Amyloid beta-Peptides - genetics
  • Amyloid Precursor Protein Secretases
  • Animals
  • Aspartic Acid Endopeptidases
  • Biological and medical sciences
  • Cell Line
  • Endopeptidases - chemistry
  • Endopeptidases - metabolism
  • Fundamental and applied biological sciences. Psychology
  • Humans
  • Membrane Proteins - chemistry
  • Membrane Proteins - deficiency
  • Membrane Proteins - genetics
  • Membrane Proteins - metabolism
  • Mice
  • Models, Biological
  • Molecular and cellular biology
  • Molecular genetics
  • Multiprotein Complexes - chemistry
  • Multiprotein Complexes - metabolism
  • Presenilin-1
  • Presenilin-2
  • Protein Binding
  • Substrate Specificity
  • Translation. Translation factors. Protein processing
ispartof: Nature, 2006, Vol.440 (7088), p.1208-1212
description: The presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref. 5) form a series of high-molecular-mass, membrane-bound protein complexes that are necessary for gamma-secretase and epsilon-secretase cleavage of selected type 1 transmembrane proteins, including the amyloid precursor protein, Notch and cadherins. Modest cleavage activity can be generated by reconstituting these four proteins in yeast and Spodoptera frugiperda (sf9) cells. However, a critical but unanswered question about the biology of the presenilin complexes is how their activity is modulated in terms of substrate specificity and/or relative activities at the gamma and epsilon sites. A corollary to this question is whether additional proteins in the presenilin complexes might subsume these putative regulatory functions. The hypothesis that additional proteins might exist in the presenilin complexes is supported by the fact that enzymatically active complexes have a mass that is much greater than predicted for a 1:1:1:1 stoichiometric complex (at least 650 kDa observed, compared with about 220 kDa predicted). To address these questions we undertook a search for presenilin-interacting proteins that differentially affected gamma- and epsilon-site cleavage events. Here we report that TMP21, a member of the p24 cargo protein family, is a component of presenilin complexes and differentially regulates gamma-secretase cleavage without affecting epsilon-secretase activity.
language: eng
source:
identifier: ISSN: 0028-0836
fulltext: no_fulltext
issn:
  • 0028-0836
  • 1476-4687
  • 1476-4679
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.0382984
LOCALfalse
PrimoNMBib
record
control
sourceidproquest_pubme
recordidTN_cdi_proquest_miscellaneous_67906547
sourceformatXML
sourcesystemPC
sourcerecordid67906547
originalsourceidFETCH-LOGICAL-p1469-31e37ca3ad4ea72a1b6971fb6e2f01bfd0b3d96242137629eff7ff580a63bdd90
addsrcrecordideNqF0c1u1DAUBWALgehQeAXkDewC1z-xY81qVLX8qAiEynp0Y18Lo8QJsVPR50K8Rp-JEUwFu66OdPTpLO5lbCfglQDVvc5Y14VAG2O3n8lTuqYg2veYV1xuJIDZbnfe01wpSHFB_XLXP2Aboa1ptOnsQ7YBkF0DnTIn7Ekp3wCgFVY_ZifCGC2ccxuGVx8-ScFT4cjnhQrlNKTM_TTOA_34k1OmXHn9ipWPU1gHrFT47c-mkF-oYiHer5XnqfLbX_-V6Gu6TvXmKXsUcSj07Jin7MvF-dXZ2-by45t3Z7vLZhbauEYJUtajwqAJrUTRG2dF7A3JCKKPAXoVnJFaCmWNdBSjjbHtAI3qQ3Bwyl7-3Z2X6ftKpe7HVDwNA2aa1rI31oFptb0Xyk5IqaS6H4J2Gpw5wOdHuPYjhf28pPHwkf3dmQ_gxRFg8TjEBbNP5Z-zVrWuVfAbUYedaw
sourcetypeAggregation Database
isCDItrue
recordtypearticle
pqid20494096
display
typearticle
titleTMP21 is a presenilin complex component that modulates γ-secretase but not ε-secretase activity
creatorFUSHENG CHEN ; HASEGAWA, Hiroshi ; WAKUTANI, Yosuke ; PARDOSSI-PIQUARD, Raphaëlle ; XUEYING RUAN ; TANDON, Anurag ; CHECLER, Frédéric ; MARAMBAUD, Philippe ; HANSEN, Kirk ; WESTAWAY, David ; ST GEORGE-HYSLOP, Peter ; FRASER, Paul ; SCHMITT-ULMS, Gerold ; KAWARAI, Toshitaka ; BOHM, Christopher ; KATAYAMA, Taiichi ; YONGJUN GU ; SANJO, Nobuo ; GLISTA, Michael ; ROGAEVA, Ekaterina
creatorcontribFUSHENG CHEN ; HASEGAWA, Hiroshi ; WAKUTANI, Yosuke ; PARDOSSI-PIQUARD, Raphaëlle ; XUEYING RUAN ; TANDON, Anurag ; CHECLER, Frédéric ; MARAMBAUD, Philippe ; HANSEN, Kirk ; WESTAWAY, David ; ST GEORGE-HYSLOP, Peter ; FRASER, Paul ; SCHMITT-ULMS, Gerold ; KAWARAI, Toshitaka ; BOHM, Christopher ; KATAYAMA, Taiichi ; YONGJUN GU ; SANJO, Nobuo ; GLISTA, Michael ; ROGAEVA, Ekaterina
descriptionThe presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref. 5) form a series of high-molecular-mass, membrane-bound protein complexes that are necessary for gamma-secretase and epsilon-secretase cleavage of selected type 1 transmembrane proteins, including the amyloid precursor protein, Notch and cadherins. Modest cleavage activity can be generated by reconstituting these four proteins in yeast and Spodoptera frugiperda (sf9) cells. However, a critical but unanswered question about the biology of the presenilin complexes is how their activity is modulated in terms of substrate specificity and/or relative activities at the gamma and epsilon sites. A corollary to this question is whether additional proteins in the presenilin complexes might subsume these putative regulatory functions. The hypothesis that additional proteins might exist in the presenilin complexes is supported by the fact that enzymatically active complexes have a mass that is much greater than predicted for a 1:1:1:1 stoichiometric complex (at least 650 kDa observed, compared with about 220 kDa predicted). To address these questions we undertook a search for presenilin-interacting proteins that differentially affected gamma- and epsilon-site cleavage events. Here we report that TMP21, a member of the p24 cargo protein family, is a component of presenilin complexes and differentially regulates gamma-secretase cleavage without affecting epsilon-secretase activity.
identifier
0ISSN: 0028-0836
1EISSN: 1476-4687
2EISSN: 1476-4679
3DOI: 10.1038/nature04667;Received15January2006;;Accepted21February2006
4PMID: 16641999
5CODEN: NATUAS
languageeng
publisherLondon: Nature Publishing
subjectAmyloid beta-Peptides - biosynthesis ; Amyloid beta-Peptides - genetics ; Amyloid Precursor Protein Secretases ; Animals ; Aspartic Acid Endopeptidases ; Biological and medical sciences ; Cell Line ; Endopeptidases - chemistry ; Endopeptidases - metabolism ; Fundamental and applied biological sciences. Psychology ; Humans ; Membrane Proteins - chemistry ; Membrane Proteins - deficiency ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; Models, Biological ; Molecular and cellular biology ; Molecular genetics ; Multiprotein Complexes - chemistry ; Multiprotein Complexes - metabolism ; Presenilin-1 ; Presenilin-2 ; Protein Binding ; Substrate Specificity ; Translation. Translation factors. Protein processing
ispartofNature, 2006, Vol.440 (7088), p.1208-1212
rights2006 INIST-CNRS
lds50peer_reviewed
links
openurl$$Topenurl_article
thumbnail$$Usyndetics_thumb_exl
backlink
0$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17735953$$DView record in Pascal Francis
1$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16641999$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0FUSHENG CHEN
1HASEGAWA, Hiroshi
2WAKUTANI, Yosuke
3PARDOSSI-PIQUARD, Raphaëlle
4XUEYING RUAN
5TANDON, Anurag
6CHECLER, Frédéric
7MARAMBAUD, Philippe
8HANSEN, Kirk
9WESTAWAY, David
10ST GEORGE-HYSLOP, Peter
11FRASER, Paul
12SCHMITT-ULMS, Gerold
13KAWARAI, Toshitaka
14BOHM, Christopher
15KATAYAMA, Taiichi
16YONGJUN GU
17SANJO, Nobuo
18GLISTA, Michael
19ROGAEVA, Ekaterina
title
0TMP21 is a presenilin complex component that modulates γ-secretase but not ε-secretase activity
1Nature
addtitleNature
descriptionThe presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref. 5) form a series of high-molecular-mass, membrane-bound protein complexes that are necessary for gamma-secretase and epsilon-secretase cleavage of selected type 1 transmembrane proteins, including the amyloid precursor protein, Notch and cadherins. Modest cleavage activity can be generated by reconstituting these four proteins in yeast and Spodoptera frugiperda (sf9) cells. However, a critical but unanswered question about the biology of the presenilin complexes is how their activity is modulated in terms of substrate specificity and/or relative activities at the gamma and epsilon sites. A corollary to this question is whether additional proteins in the presenilin complexes might subsume these putative regulatory functions. The hypothesis that additional proteins might exist in the presenilin complexes is supported by the fact that enzymatically active complexes have a mass that is much greater than predicted for a 1:1:1:1 stoichiometric complex (at least 650 kDa observed, compared with about 220 kDa predicted). To address these questions we undertook a search for presenilin-interacting proteins that differentially affected gamma- and epsilon-site cleavage events. Here we report that TMP21, a member of the p24 cargo protein family, is a component of presenilin complexes and differentially regulates gamma-secretase cleavage without affecting epsilon-secretase activity.
subject
0Amyloid beta-Peptides - biosynthesis
1Amyloid beta-Peptides - genetics
2Amyloid Precursor Protein Secretases
3Animals
4Aspartic Acid Endopeptidases
5Biological and medical sciences
6Cell Line
7Endopeptidases - chemistry
8Endopeptidases - metabolism
9Fundamental and applied biological sciences. Psychology
10Humans
11Membrane Proteins - chemistry
12Membrane Proteins - deficiency
13Membrane Proteins - genetics
14Membrane Proteins - metabolism
15Mice
16Models, Biological
17Molecular and cellular biology
18Molecular genetics
19Multiprotein Complexes - chemistry
20Multiprotein Complexes - metabolism
21Presenilin-1
22Presenilin-2
23Protein Binding
24Substrate Specificity
25Translation. Translation factors. Protein processing
issn
00028-0836
11476-4687
21476-4679
fulltextfalse
rsrctypearticle
creationdate2006
recordtypearticle
recordideNqF0c1u1DAUBWALgehQeAXkDewC1z-xY81qVLX8qAiEynp0Y18Lo8QJsVPR50K8Rp-JEUwFu66OdPTpLO5lbCfglQDVvc5Y14VAG2O3n8lTuqYg2veYV1xuJIDZbnfe01wpSHFB_XLXP2Aboa1ptOnsQ7YBkF0DnTIn7Ekp3wCgFVY_ZifCGC2ccxuGVx8-ScFT4cjnhQrlNKTM_TTOA_34k1OmXHn9ipWPU1gHrFT47c-mkF-oYiHer5XnqfLbX_-V6Gu6TvXmKXsUcSj07Jin7MvF-dXZ2-by45t3Z7vLZhbauEYJUtajwqAJrUTRG2dF7A3JCKKPAXoVnJFaCmWNdBSjjbHtAI3qQ3Bwyl7-3Z2X6ftKpe7HVDwNA2aa1rI31oFptb0Xyk5IqaS6H4J2Gpw5wOdHuPYjhf28pPHwkf3dmQ_gxRFg8TjEBbNP5Z-zVrWuVfAbUYedaw
startdate2006
enddate2006
creator
0FUSHENG CHEN
1HASEGAWA, Hiroshi
2WAKUTANI, Yosuke
3PARDOSSI-PIQUARD, Raphaëlle
4XUEYING RUAN
5TANDON, Anurag
6CHECLER, Frédéric
7MARAMBAUD, Philippe
8HANSEN, Kirk
9WESTAWAY, David
10ST GEORGE-HYSLOP, Peter
11FRASER, Paul
12SCHMITT-ULMS, Gerold
13KAWARAI, Toshitaka
14BOHM, Christopher
15KATAYAMA, Taiichi
16YONGJUN GU
17SANJO, Nobuo
18GLISTA, Michael
19ROGAEVA, Ekaterina
generalNature Publishing
scope
0IQODW
1CGR
2CUY
3CVF
4ECM
5EIF
6NPM
77SS
88FD
9FR3
10P64
11RC3
127U5
13L7M
147X8
sort
creationdate2006
titleTMP21 is a presenilin complex component that modulates γ-secretase but not ε-secretase activity
authorFUSHENG CHEN ; HASEGAWA, Hiroshi ; WAKUTANI, Yosuke ; PARDOSSI-PIQUARD, Raphaëlle ; XUEYING RUAN ; TANDON, Anurag ; CHECLER, Frédéric ; MARAMBAUD, Philippe ; HANSEN, Kirk ; WESTAWAY, David ; ST GEORGE-HYSLOP, Peter ; FRASER, Paul ; SCHMITT-ULMS, Gerold ; KAWARAI, Toshitaka ; BOHM, Christopher ; KATAYAMA, Taiichi ; YONGJUN GU ; SANJO, Nobuo ; GLISTA, Michael ; ROGAEVA, Ekaterina
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-p1469-31e37ca3ad4ea72a1b6971fb6e2f01bfd0b3d96242137629eff7ff580a63bdd90
rsrctypearticles
prefilterarticles
languageeng
creationdate2006
topic
0Amyloid beta-Peptides - biosynthesis
1Amyloid beta-Peptides - genetics
2Amyloid Precursor Protein Secretases
3Animals
4Aspartic Acid Endopeptidases
5Biological and medical sciences
6Cell Line
7Endopeptidases - chemistry
8Endopeptidases - metabolism
9Fundamental and applied biological sciences. Psychology
10Humans
11Membrane Proteins - chemistry
12Membrane Proteins - deficiency
13Membrane Proteins - genetics
14Membrane Proteins - metabolism
15Mice
16Models, Biological
17Molecular and cellular biology
18Molecular genetics
19Multiprotein Complexes - chemistry
20Multiprotein Complexes - metabolism
21Presenilin-1
22Presenilin-2
23Protein Binding
24Substrate Specificity
25Translation. Translation factors. Protein processing
toplevelpeer_reviewed
creatorcontrib
0FUSHENG CHEN
1HASEGAWA, Hiroshi
2WAKUTANI, Yosuke
3PARDOSSI-PIQUARD, Raphaëlle
4XUEYING RUAN
5TANDON, Anurag
6CHECLER, Frédéric
7MARAMBAUD, Philippe
8HANSEN, Kirk
9WESTAWAY, David
10ST GEORGE-HYSLOP, Peter
11FRASER, Paul
12SCHMITT-ULMS, Gerold
13KAWARAI, Toshitaka
14BOHM, Christopher
15KATAYAMA, Taiichi
16YONGJUN GU
17SANJO, Nobuo
18GLISTA, Michael
19ROGAEVA, Ekaterina
collection
0Pascal-Francis
1Medline
2MEDLINE
3MEDLINE (Ovid)
4MEDLINE
5MEDLINE
6PubMed
7Entomology Abstracts (Full archive)
8Technology Research Database
9Engineering Research Database
10Biotechnology and BioEngineering Abstracts
11Genetics Abstracts
12Solid State and Superconductivity Abstracts
13Advanced Technologies Database with Aerospace
14MEDLINE - Academic
jtitleNature
delivery
delcategoryRemote Search Resource
fulltextno_fulltext
addata
au
0FUSHENG CHEN
1HASEGAWA, Hiroshi
2WAKUTANI, Yosuke
3PARDOSSI-PIQUARD, Raphaëlle
4XUEYING RUAN
5TANDON, Anurag
6CHECLER, Frédéric
7MARAMBAUD, Philippe
8HANSEN, Kirk
9WESTAWAY, David
10ST GEORGE-HYSLOP, Peter
11FRASER, Paul
12SCHMITT-ULMS, Gerold
13KAWARAI, Toshitaka
14BOHM, Christopher
15KATAYAMA, Taiichi
16YONGJUN GU
17SANJO, Nobuo
18GLISTA, Michael
19ROGAEVA, Ekaterina
formatjournal
genrearticle
ristypeJOUR
atitleTMP21 is a presenilin complex component that modulates γ-secretase but not ε-secretase activity
jtitleNature
addtitleNature
date2006
risdate2006
volume440
issue7088
spage1208
epage1212
pages1208-1212
issn0028-0836
eissn
01476-4687
11476-4679
codenNATUAS
abstractThe presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref. 5) form a series of high-molecular-mass, membrane-bound protein complexes that are necessary for gamma-secretase and epsilon-secretase cleavage of selected type 1 transmembrane proteins, including the amyloid precursor protein, Notch and cadherins. Modest cleavage activity can be generated by reconstituting these four proteins in yeast and Spodoptera frugiperda (sf9) cells. However, a critical but unanswered question about the biology of the presenilin complexes is how their activity is modulated in terms of substrate specificity and/or relative activities at the gamma and epsilon sites. A corollary to this question is whether additional proteins in the presenilin complexes might subsume these putative regulatory functions. The hypothesis that additional proteins might exist in the presenilin complexes is supported by the fact that enzymatically active complexes have a mass that is much greater than predicted for a 1:1:1:1 stoichiometric complex (at least 650 kDa observed, compared with about 220 kDa predicted). To address these questions we undertook a search for presenilin-interacting proteins that differentially affected gamma- and epsilon-site cleavage events. Here we report that TMP21, a member of the p24 cargo protein family, is a component of presenilin complexes and differentially regulates gamma-secretase cleavage without affecting epsilon-secretase activity.
copLondon
pubNature Publishing
pmid16641999
doi10.1038/nature04667;Received15January2006;;Accepted21February2006