真核生物翻訳開始因子5、翻訳開始因子5

関: eIF-5、eIF5、eukaryotic translation initiation factor 5

WordNet

be a contributing factor; "make things factor into a companys profitability"
any of the numbers (or symbols) that form a product when multiplied together
an independent variable in statistics
anything that contributes causally to a result; "a number of factors determined the outcome"
consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
a concept whose truth can be proved; "scientific hypotheses are not facts"
a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
the act of starting something for the first time; introducing something new; "she looked forward to her initiation as an adult"; "the foundation of a new scientific society" (同)founding, foundation, institution, origination, creation, innovation, introduction, instauration
a formal entry into an organization or position or office; "his initiation into the club"; "he was ordered to report for induction into the army"; "he gave a speech as part of his installation into the hall of fame" (同)induction, installation
having cells with `good or membrane-bound nuclei (同)eucaryotic

PrepTutorEJDIC

(…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
〈U〉開始;創業 / 〈U〉入会,入門;〈C〉入会(入門)式 / 〈U〉手ほどき,伝授

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/04/16 20:35:31」(JST)

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Eukaryotic initiation factors (eIF) are proteins involved in the initiation phase of eukaryotic translation. They function in forming a complex with the 40S ribosomal subunit and Met-tRNA_i called the 43S preinitation complex (PIC), recognizing the 5' cap structure of mRNA and recruiting the 43S PIC to mRNA, promoting ribosomal scanning of mRNA and regulating recognition of the AUG initiation codon, and joining of the 60S ribosomal subunit to create the 80S ribosome. There exist many more eukaryotic initiation factors than prokaryotic initiation factors due to greater biological complexity of eukaryotic cells.

The protein RLI is known to have an essential, probably catalytic role in the formation of initiation complexes as well.

eIF4 (eIF4F)

Main article: Eif4a

The eIF4 initiation factors include eIF4A, eIF4B, eIF4E, and eIF4G. eIF4F is often used to refer to the complex of eIF4A, eIF4E, and eIF4G.

eIF4G is a scaffolding protein that interacts with eIF3 (see below), as well as the other members of the eIF4F complex. eIF4E recognizes and binds to the 5' cap structure of mRNA, while eIF4G binds to Poly(A)-binding protein, which binds the poly(A) tail, circularizing and activating the bound mRNA.

eIF4A – a DEAD box RNA helicase – is important for resolving mRNA secondary structures. eIF4B contains two RNA-binding domains – one non-specifically interacts with mRNA, whereas the second specifically binds the 18S portion of the small ribosomal subunit. It acts as an anchor, as well as a critical co-factor for eIF4A. It is a substrate of S6K, and, when phosphorylated, it promotes the formation of the pre-initiation complex. In vertebrates, eIF4H is an additional initiation factor with similar function to eIF4B.

eIF1 & eIF3

eIF1, eIF1A, and eIF3 all bind to the ribosome subunit-mRNA complex. They have been implicated in preventing the large ribosomal subunit from binding the small subunit before it is ready to commence elongation.

In mammals, eIF3 is the largest scaffolding initiation factor, made up of 13 subunits (a-m). It is roughly ~750 kDa and it controls the assembly of 40S ribosomal subunit on mRNA that have a 5' cap or an IRES. eIF3 uses the eIF4F complex or IRES (Internal Ribosomal Entry Site) from viruses to position the mRNA strand near the exit site of the 40S ribosome subunit, thus promoting the assembly of the pre-initiation complex.

In many cancers, eIF3 is overexpressed. Under serum-deprived conditions (inactive state), eIF3 is bound to S6K1. On stimulation by either mitogens, growth factors, or drugs, mTOR/Raptor complex gets activated and, in turn, binds and phosphorylates S6K1 on T389 (linker region), causing a conformational change that causes the kinase S6K1 to dissociate from eIF3. The T389 phosphorylated S6k1 is then further phosphorylated by PDK1 on T229. This second phosphorylation fully activates the S6K1 kinase, which can then phosphorylate eIF4B, S6, and other protein targets.

Mammalian 17-kDa eukaryotic initiation factor, eIF1A (formerly designated eIF-4C), is essential for transfer of the initiator Met-tRNAf (as Met-tRNAf·eIF2·GTP ternary complex) to 40 S ribosomal subunits in the absence of mRNA to form the 40 S preinitiation complex (40 S·Met-tRNAf·eIF2·GTP). Furthermore, eIF1A acts catalytically in this reaction to mediate highly efficient transfer of the Met-tRNAf·eIF2·GTP ternary complex to 40 S ribosomal subunits. The 40 S complex formed is free of eIF1A which indicates that its role in 40 S preinitiation complex formation is not to stabilize the binding of Met-tRNAf to 40 S ribosomes. Additionally, the eIF1A-mediated 40 S initiation complex formed in the presence of AUG codon efficiently joins 60 S ribosomal subunits in an eIF5-dependent reaction to form a functional 80 S initiation complex. Though found in some reports, eIF1A probably plays no role either in the subunit joining reaction or in the generation of ribosomal subunits from 80 S ribosomes. The major function of eIF1A is to mediate the transfer of Met-tRNAf to 40 S ribosomal subunits to form the 40 S preinitiation complex. ^[1]

eIF2

See main article at EIF-2

eIF2 is a GTP-binding protein responsible for bringing the initiator tRNA to the P-site of the pre-initiation complex. It has specificity for the methionine-charged initiator tRNA, which is distinct from other methionine-charged tRNAs specific for elongation of the polypeptide chain. Once it has placed the initiator tRNA on the AUG start codon in the P-site, it hydrolyzes GTP into GDP, and dissociates. This hydrolysis, also signals for the dissociation of eIF3, eIF1, and eIF1A, and allows the large subunit to bind. This signals the beginning of elongation.

eIF2 has three subunits, eIF2-α, β, and γ. The former is of particular importance for cells that may need to turn off protein synthesis globally. When phosphorylated, it sequesters eIF2B (not to be confused with beta), a GEF. Without this GEF, GDP cannot be exchanged for GTP, and translation is repressed.

eIF2α-induced translation repression occurs in reticulocytes when starved for iron. In addition, protein kinase R (PKR) phosphorylates eIF2α when dsRNA is detected in many multicellular organisms, leading to cell death.

eIF5 & eIF5B

eIF5A is a GTPase-activating protein, which helps the large ribosomal subunit associate with the small subunit. It is required for GTP-hydrolysis by eIF2 and contains the unusual amino acid hypusine.^[2]

eIF5B is a GTPase, and is involved in assembly of the full ribosome (which requires GTP hydrolysis).

eIF6

Main article: eIF6

eIF6 performs the same inhibition of ribosome assembly as eIF3, but binds with the large subunit.

References

^ Umadas Maitra, Jayanta Chaudhuri; Jayanta Chaudhuri, Kausik Si (21). "Function of Eukaryotic Translation Initiation Factor 1A (eIF1A) (Formerly Called eIF-4C) in Initiation of Protein Synthesis". The Journal of BIological Chemistry 272 (12): 7883–7891. doi:10.1074/jbc.272.12.7883. http://www.jbc.org/content/272/12/7883.full.pdf+html. Retrieved 19 February 2012.
^ Park, Myung Hee (February 2006). "The Post-Translational Synthesis of a Polyamine-Derived Amino Acid, Hypusine, in the Eukaryotic Translation Initiation Factor 5A (eIF5A)". Journal of Biochemistry 139 (2): 161–9. doi:10.1093/jb/mvj034. PMC 2494880. PMID 16452303. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2494880.

External links

Fraser, CS; Doudna, JA (2007). "Structural and mechanistic insights into hepatitis C viral translation initiation". Nature reviews. Microbiology 5 (1): 29–38. doi:10.1038/nrmicro1558. PMID 17128284.
Malys N, McCarthy JEG (2011). "Translation initiation: variations in the mechanism can be anticipated". Cellular and Molecular Life Sciences 68 (6): 991–1003. doi:10.1007/s00018-010-0588-z. PMID 21076851.
MeSH Eukaryotic+Initiation+Factors

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English Journal

Knockdown expression of eukaryotic initiation factor 5 C-terminal domain containing protein extends lifespan in Drosophila melanogaster.

Wang D1, Cui Y2, Jiang Z3, Xie W4.
Biochemical and biophysical research communications.Biochem Biophys Res Commun.2014 Apr 4;446(2):465-9. doi: 10.1016/j.bbrc.2014.02.133. Epub 2014 Mar 12.
Inhibition of translation by mutations of a growing number of genes involved in protein synthesis could extend healthy lifespan in yeast, worm, fly and mouse as well. These genes vary from translation initiation factors to structural components of ribosomes and ribosomal RNA processing factors. ECP
PMID 24613847

N-terminal hydrophobic amino acids of activating transcription factor 5 (ATF5) protein confer interleukin 1β (IL-1β)-induced stabilization.

Abe T1, Kojima M, Akanuma S, Iwashita H, Yamazaki T, Okuyama R, Ichikawa K, Umemura M, Nakano H, Takahashi S, Takahashi Y.
The Journal of biological chemistry.J Biol Chem.2014 Feb 14;289(7):3888-900. doi: 10.1074/jbc.M113.491217. Epub 2013 Dec 30.
Activating transcription factor 5 (ATF5) is a stress-response transcription factor that responds to amino acid limitation and exposure to cadmium chloride (CdCl2) and sodium arsenite (NaAsO2). The N-terminal amino acids contribute to the destabilization of the ATF5 protein in steady-state conditions
PMID 24379400

Enhanced eIF1 binding to the 40S ribosome impedes conformational rearrangements of the preinitiation complex and elevates initiation accuracy.

Martin-Marcos P, Nanda JS, Luna RE, Zhang F, Saini AK, Cherkasova VA, Wagner G, Lorsch JR, Hinnebusch AG.
RNA (New York, N.Y.).RNA.2014 Feb;20(2):150-67. doi: 10.1261/rna.042069.113. Epub 2013 Dec 13.
In the current model of translation initiation by the scanning mechanism, eIF1 promotes an open conformation of the 40S subunit competent for rapidly loading the eIF2·GTP·Met-tRNAi ternary complex (TC) in a metastable conformation (POUT) capable of sampling triplets entering the P site while block
PMID 24335188

Japanese Journal

"Hybrid Exercise" Prevents Muscle Atrophy in Association with a Distinct Gene Expression Pattern

MATSUGAKI TORU,SHIBA NAOTO,KOHNO SHOHEI,NIKAWA TAKESHI,HIRASAKA KATSUYA,OKUMURA YUUSHI,ISHIDOH KAZUMI,SOEJIMA TAKASHI,YOSHIMITSU KAZUHIRO,NAGATA KENSEI
The Kurume Medical Journal 57(4), 101-108, 2010
… In particular, gene ontology analysis revealed that hybrid exercise induced significantly higher expression of eukaryotic translation initiation factor 5A (EIFSA), peroxisomal biogenesis factor 6 (PEX6) and histone cluster 1 H4 (HIST1H4), compared with electrical stimulation alone. …
NAID 130001055545

Doxorubicin Induces Apoptosis in H9c2 Cardiomyocytes: Role of Overexpressed Eukaryotic Translation Initiation Factor 5A

Tan Xiao,Wang Di-bin,Lu Xiang [他],Wei Hui,Zhu Rong,Zhu Shu-shu,Jiang Hai,Yang Zhi-jian
Biological and Pharmaceutical Bulletin 33(10), 1666-1672, 2010
… Eukaryotic translation initiation factor 5A (eIF5A) is a ubiquitously expressed multifunctional protein that interacts with a range of ligands and is implicated in cell signaling. … However, there has been no direct evidence for the critical involvement of eIF5A in doxorubicin-induced apoptosis. …
NAID 130000402359

The Post-Translational Synthesis of a Polyamine-Derived Amino Acid, Hypusine, in the Eukaryotic Translation Initiation Factor 5A (eIF5A)

Park Myung Hee
The journal of biochemistry 139(2), 161-169, 2006-02-01
NAID 10018847347

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リンク元	「真核生物翻訳開始因子5」「eIF5」「eukaryotic translation initiation factor 5」「翻訳開始因子5」
関連記事	「initiation」「fact」「factor」「eukaryotic」