Nature20March2008Volume452Number7185pp253386 NMNAT_2
New Human Famsbase for New Human Famsbase for Nature 20 March 2008 Volume
452 Number 7185, pp253-386 NMNAT_2
wwwpdfamscomindexjahtml
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Hideaki Umeyama, Ph.D., Professor
School of Pharmacy, Kitasato University
5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
phone : +81-3-5791-6330
fax : +81-3-3446-9553
e-mail:umeyamah@pharm.kitasato-u.ac.jp
港区白金５－９－１
北里大学薬学部教授（理化学研究所客員主管研究員）
梅山秀明
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ENSEMBL Homo sapiens (human)
hsap0
43797
-
Metazoa Chordata
ENSEMBL Homo sapiens (human)
137746 -
Metazoa Chordata
H-Invitational Homo sapiens (human)
hsap1
hsap2
28983
-
Metazoa Chordata
NCBI Homo sapiens (cDNA)
-
Metazoa Chordata
Kazusa
huge0
2038
http://apr2007.archive.ensembl.org/Homo_sapiens/index.html
http://www.h-invitational.jp/
http://hinv.ddbj.nig.ac.jp/index-j.html
http://www.ncbi.nlm.nih.gov/genome/guide/human/
http://www.kazusa.or.jp/huge/
New Human Famsbase for Nature 20 March 2008 Volume 452 Number 7185, pp253-386
NMNAT
Nature 20 March 2008 Volume 452 Number 7185, pp253-386 NMNAT
Translational control of the innate immune response through IRF-7 p323
Production of type-I interferon is regulated by the transcription factor
IRF-7. This paper shows that IRF 7 is negatively regulated by
translational repressor proteins 4E BP1 and 4E BP2. Viral infection
promotes mTOR-mediated phosphorylation of the repressor proteins and
allows type I interferon production to proceed.
Rodney Colina et al.
doi:10.1038/nature06730
First paragraph | Full Text | PDF
See also: Editor's summary
Abstract
Article
Nature 452, 323-328 (20 March 2008) | doi:10.1038/nature06730; Received
28 November 2007; Accepted 25 January 2008; Published online 13 February
2008
IRF-7 を介した自然免疫応答の翻訳による制御
. (Title in English; ).Rodney Colina1,4, Mauro Costa-Mattioli1,4, Ryan
J. O. Dowling1, Maritza Jaramillo1, Lee-Hwa Tai2, Caroline J.
Breitbach3, Yvan Martineau1, Ola Larsson1, Liwei Rong1, Yuri V.
Svitkin1, Andrew P. Makrigiannis2, John C. Bell3 & Nahum Sonenberg1
Department of Biochemistry and McGill Cancer Center, McGill University,
Montreal, Quebec H3G 1Y6, Canada
Institut de Recherches Cliniques de Montréal, Laboratory of Molecular
Immunology, Université de Montréal, Montréal, Quebec H2W 1R7, Canada
Ottawa Health Research Institute, Ottawa, Ontario K1H 8L6, Canada
These authors contributed equally to this work.
Correspondence to: Mauro Costa-Mattioli1,4Nahum Sonenberg1
Correspondence and requests for materials should be addressed to N.S.
(Email: nahum.sonenberg@mcgill.ca) or M.C.-M. (Email: mauro.costamattioli@mail.mcgill.ca).
Top of pageAbstractI 型インターフェロン（インターフェロン（IFN）-αおよび
IFN-β）のようなサイトカインの転写活性化は、抗ウイルス防御の最前線となってい
る。本論文では、I 型 IFN の産生誘導に翻訳制御が重要であることを示す。翻訳リプレ
ッサー4E-BP1 および 4E-BP2 を欠損するマウス胚性繊維芽細胞では、I 型 IFN 産生を引
き起こす閾値が低くなる。その結果、脳心筋炎ウイルス、水疱性口内炎ウイルス、イ
ンフルエンザウイルス、およびシンドビスウイルスの複製が大幅に抑制される。また
、 4E-BP1 および 4E-BP2 （別名はそれぞれ Eif4ebp1 と Eif4ebp2 ）遺伝子の両
方がノックアウトされたマウスは、水疱性口内炎ウイルス感染に耐性があり、この耐
性は形質細胞様樹状細胞での I 型 IFN 産生の亢進および肺での IFN によって制御される
遺伝子発現と相関している。 4E-BP1−/−4E-BP2−/− ダブルノックアウトマウスの胚
性繊維芽細胞での I 型 IFN 応答の亢進は、インターフェロン制御因子 7（ Irf7 ）メッ
センジャーRNA 翻訳の上方制御によって引き起こされる。これらの知見は、4E-BP 群が
I 型 IFN 産生の負の調節因子の役割をもち、 Irf7 mRNA の翻訳抑制を介して働くこと
を明らかにしている。
Top of page
4E-BP1−/−4E-BP2−/− ダブルノックアウトマウスの胚性繊維芽細胞での I 型 IFN 応答の
亢進は、インターフェロン制御因子 7（ Irf7 ）メッセンジャーRNA 翻訳の上方制御
によって引き起こされる。これらの知見は、4E-BP 群が I 型 IFN 産生の負の調節因子の
役割をもち、 Irf7 mRNA の翻訳抑制を介して働くことを明らかにしている。
インターフェロン制御因子 7（ Irf7 ）
4E-BP1 および 4E-BP2 （別名はそれぞれ Eif4ebp1 と Eif4ebp2 ）遺伝子
4E-BP1
Eif4ebp1
3:
Q13541
Reports
BLink, Conserved Domains, Links
Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) (eIF4E-binding
protein 1) (Phosphorylated heat- and acid-stable protein regulated by insulin 1)
(PHAS-I)
gi|34921508|sp|Q13541.3|4EBP1_HUMAN[34921508]
LOCUS
Q13541
118 aa
linear
PRI
15-JAN-2008
DEFINITION Eukaryotic translation initiation factor 4E-binding protein
1
(4E-BP1) (eIF4E-binding protein 1) (Phosphorylated heat- and
acid-stable protein regulated by insulin 1) (PHAS-I).
ACCESSION
Q13541
VERSION
DBSOURCE
Q13541.3 GI:34921508
swissprot: locus 4EBP1_HUMAN, accession Q13541;
class: standard.
extra accessions:Q6IBN3
created: Sep 19, 2003.
sequence updated: Jan 23, 2007.
annotation updated: Jan 15, 2008.
COMMENT
On or before Jan 24, 2006 this sequence version replaced
gi:74721972, gi:1079483.
[FUNCTION] Regulates eIF4E activity by preventing its assembly
into
the eIF4F complex. Mediates the regulation of protein
translation
by hormones, growth factors and other stimuli that signal
through
the MAP kinase pathway.
[SUBUNIT] Nonphosphorylated EIF4EBP1 competes with
EIF4G1/EIF4G3 to
interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and
MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the
complex allowing EIF4G1/EIF4G3 to bind and consequent
initiation of
translation. Rapamycin can attenuate insulin stimulation,
mediated
by FKBPs.
[INTERACTION] P06730:EIF4E; NbExp=4; IntAct=EBI-74090,
EBI-73440;
O60573:EIF4E2; NbExp=1; IntAct=EBI-74090, EBI-398610;
Q80ZJ3:Eif4e2
(xeno); NbExp=1; IntAct=EBI-74090, EBI-934970;
Q9BSL1:UBADC1;
NbExp=1; IntAct=EBI-74090, EBI-749370.
[PTM] Phosphorylated on serine and threonine residues in
response
to insulin, EGF and PDGF. Phosphorylated upon DNA damage,
probably
by ATM or ATR.
[SIMILARITY] Belongs to the eIF4E-binding protein family.
FEATURES
Location/Qualifiers
source
1..118
/organism="Homo sapiens"
/db_xref="taxon:9606"
gene
1..118
/gene="EIF4EBP1"
Protein
1..118
/gene="EIF4EBP1"
/product="Eukaryotic translation initiation factor
4E-binding protein 1"
>gi|34921508|sp|Q13541.3|4EBP1_HUMAN Eukaryotic translation initiation
factor 4E-binding protein 1 (4E-BP1) (eIF4E-binding protein 1)
(Phosphorylated heat- and acid-stable protein regulated by insulin 1)
(PHAS-I)
MSGGSSCSQTPSRAIPATRRVVLGDGVQLPPGDYSTTPGGTLFSTTPGGTRIIYDRKFLMECRNSPVTKT
PPRDLPTIPGVTSPSSDEPPMEASQSHLRNSPEDKRAGGEESQFEMDI
4E-BP2
Eif4ebp2
Items 1 - 2 of 2
One page.
1:
Q13542 Reports
BLink, Conserved Domains, Links
Eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2)
(eIF4E-binding protein 2)
gi|34921510|sp|Q13542.1|4EBP2_HUMAN[34921510]
LOCUS
Q13542
120 aa
linear
PRI
13-NOV-2007
DEFINITION Eukaryotic translation initiation factor 4E-binding protein
2
(4E-BP2) (eIF4E-binding protein 2).
ACCESSION
Q13542
VERSION
Q13542.1 GI:34921510
DBSOURCE
swissprot: locus 4EBP2_HUMAN, accession Q13542;
COMMENT
class: standard.
created: Sep 19, 2003.
sequence updated: Nov 1, 1996.
annotation updated: Nov 13, 2007.
On Mar 15, 2005 this sequence version replaced gi:2134670.
[FUNCTION] Regulates eIF4E activity by preventing its assembly
into
the eIF4F complex. Mediates the regulation of protein
translation
by hormones, growth factors and other stimuli that signal
through
the MAP kinase pathway.
[SUBUNIT] Nonphosphorylated EIF4EBP2 interacts with EIF4E.
[INTERACTION] P06730:EIF4E; NbExp=1; IntAct=EBI-935137,
EBI-73440;
Q80ZJ3:Eif4e2 (xeno); NbExp=1; IntAct=EBI-935137,
EBI-934970.
[PTM] Phosphorylated on serine and threonine residues in
response
to insulin, EGF and PDGF.
[SIMILARITY] Belongs to the eIF4E-binding protein family.
FEATURES
Location/Qualifiers
source
1..120
/organism="Homo sapiens"
/db_xref="taxon:9606"
gene
1..120
/gene="EIF4EBP2"
Protein
1..120
/gene="EIF4EBP2"
/product="Eukaryotic translation initiation factor
4E-binding protein 2"
>gi|34921510|sp|Q13542.1|4EBP2_HUMAN Eukaryotic translation initiation
factor 4E-binding protein 2 (4E-BP2) (eIF4E-binding protein 2)
MSSSAGSGHQPSQSRAIPTRTVAISDAAQLPHDYCTTPGGTLFSTTPGGTRIIYDRKFLLDRRNSPMAQT
PPCHLPNIPGVTSPGTLIEDSKVEVNNLNNLNNHDRKHAVGDDAQFEMDI