真核起始因子3

eIF3（eukaryotic initiation factor 3，真核起始因子3）是最大的真核起始因子，在哺乳動物細胞中，其分子量超過了600KDa。eIF3是真核翻譯起始進程中起着核心作用。^[1]例如，eIF3可以使eIF2·GTP·Met-tRNA_i三聯體複合物穩定地結合到40S核糖體亞基上，並促使43S前起始複合物的形成；它能夠通過促進mRNA與40S亞基結合；而且，它還可以與游離的40S亞基結合，影響40S亞基與60S亞基及其他eIF的結合或解離等等。^[2]

eIF3是一個結構中心，可以與不同的真核起始因子以及RNA結合來調控整個翻譯起始進程。^[3]

eIF3是一個多亞基複合物，也是最複雜的起始因子。哺乳動物中存在13種不同的亞基（a、b、c、d、e、f、g、h、i、j、k、l和m），而部分酵母中只有6個（a、b、c、g、i、j）。^[3]^[2]

功能

eIF3參與了真核翻譯起始進程中大多數的反應。^[1]eIF3可以與游離的40S核糖體亞基結合，阻止40S亞基與60S核糖體亞基的直接結合，從而防止形成無翻譯活性的80S核糖體；通過與eIF2的相互作用，eIF3可以使eIF2·GTP·Met-tRNA_i三聯體複合物穩定地結合到40S亞基上，並促使43S前起始複合物的形成；eIF3可能通過與eIF4G的相互作用^[4]^[5]來或者通過直接與mRNA結合，促進mRNA與40S亞基結合，從而幫助48S前起始複合物的形成。eIF3也在重起始（reinitiation）的掃描和起始AUG密碼子的選擇中發揮作用。^[6]^[7]

除了在翻譯起始過程中發揮核心作用，eIF3還被發現參與翻譯過程以及細胞周期的調控。^[8]^[9]通過調節不同類型的mRNA的翻譯起始，eIF3就可能選擇性地調控蛋白的合成，從而對細胞的生長進行調控。而eIF3的a、b、e和k^[10]亞基都可能參與細胞周期調控。

亞基組成和結構

eIF3是一個多亞基複合物，目前發現的亞基共有13個，但不同的物種所含的亞基數量差異很大，例如哺乳動物中含有所有的13個亞基，而釀酒酵母中只含有6個亞基。eIF3許多亞基中都含有PCI和MPN結構域，這兩類結構域都是參與蛋白-蛋白相互作用的；而eIF3c和3g中出現的RNA識別（RNA recognition motif，RRM）結構域則可能是參與RNA的結合。這些結構域提示eIF3是一個結構中心，通過與不同的起始因子以及RNA結合來調控整個翻譯起始進程。^[2]儘管在亞基數目上有很大區別，但在酵母和人中都發現a、b、c、g和i亞基能夠形成一個核心複合物，這5個亞基的氨基酸序列相當保守，而且它們對於酵母的生長都是必需的，^[11]^[12]因此這5個亞基就被稱為核心亞基，而其他亞基則被稱為非核心亞基。

**eIF3亞基組成**^[3]^[13]
亞基	包含結構域	功能
a	PCI	與40S亞基和eIF4F結合；參與多因子複合物（MFC）聚合；參與招募三聯體和mRNA
b	RRM	與40S亞基結合；參與MFC聚合、招募三聯體和mRNA；參與掃描起始密碼子
c	PCI	與40S亞基結合；參與MFC聚合、招募三聯體和mRNA、AUG密碼子識別
d	-	可能為mTOR和S6K1蛋白提供結合位點
e	PCI	與eIF4B和CaMV TAV（重起始中）結合
f	MPN	-
g	RRM、鋅指	-
h	MPN	-
i	WD40	-
j	-	與40S亞基結合；參與MFC聚合
k^[14]	PCI	與40S亞基結合
l	-	-
m	PCI	-

參考資料

[1]
（英文）Pain VM. Initiation of protein synthesis in eukaryotic cells. Eur J Biochem. 1996, 236: 747–71.
[2]
（英文）Hershey JWB & Merrick WC. The pathway and mechanism of initiation of protein synthesis. Nahum Sonenberg, John W. B. Hershey, Michael Mathews (編). Translational Control of Gene Expression. Cold Spring Harbor Laboratory Press. 2000.
[3]
（英文）Hinnebusch AG. eIF3: a versatile scaffold for translation initiation complexes. Trends Biochem Sci. 2006, 31: 553–62. PMID 16920360.
[4]
（英文）Korneeva, N.L.; et al. Mutually cooperative binding of eukaryotic translation initiation factor (eIF) 3 and eIF4A to human eIF4G-1. J Biol Chem. 2000, 275: 41369–76.
[5]
（英文）Lamphear, B.J.; et al. Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation. J Biol Chem. 1995, 270: 21975–83.
[6]
（英文）Park, H.S.; et al. Eucaryotic initiation factor 4B controls eIF3-mediated ribosomal entry of viral reinitiation factor. Embo J. 2004, 23: 1381–91.
[7]
（英文）Park, H.S.; et al. A plant viral "reinitiation" factor interacts with the host translational machinery. Cell. 2001, 106: 723–33.
[8]
（英文）Dong, Z. and Zhang, J.T. Initiation factor eIF3 and regulation of mRNA translation, cell growth, and cancer. Crit Rev Oncol Hematol. 2006, 59: 169–80.
[9]
（英文）Pyronnet, S. and Sonenberg, N. Cell-cycle-dependent translational control. Curr Opin Genet Dev. 2001, 11: 13–8.
[10]
（英文）Shen, X.; et al. Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3. FEBS Lett. 2004, 573: 139–46.
[11]
（英文）Phan, L.; et al. Identification of a translation initiation factor 3 (eIF3) core complex, conserved in yeast and mammals, that interacts with eIF5. Mol Cell Biol. 1998, 18 (8): 4935–46.
[12]
（英文）Fraser, C.S.; et al. The j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro. J Biol Chem. 2004, 279 (10): 8946–56.
[13]
（英文）Burks, E.A.; et al. Plant initiation factor 3 subunit composition resembles mammalian initiation factor 3 and has a novel subunit. J Biol Chem. 2001, 276 (3): 2122–31.
[14]
（英文）Scheel, H. and Hofmann, K. Prediction of a common structural scaffold for proteasome lid, COP9-signalosome and eIF3 complexes. BMC Bioinformatics. 2005, 6 (1): 71.

參見

真核起始因子
支架蛋白

[Pain-1] [1]
（英文）Pain VM. Initiation of protein synthesis in eukaryotic cells. Eur J Biochem. 1996, 236: 747–71.

[Hershey-2] [2]
（英文）Hershey JWB & Merrick WC. The pathway and mechanism of initiation of protein synthesis. Nahum Sonenberg, John W. B. Hershey, Michael Mathews (編). Translational Control of Gene Expression. Cold Spring Harbor Laboratory Press. 2000.

[Hinnebusch-3] [3]
（英文）Hinnebusch AG. eIF3: a versatile scaffold for translation initiation complexes. Trends Biochem Sci. 2006, 31: 553–62. PMID 16920360.

[4] [4]
（英文）Korneeva, N.L.; et al. Mutually cooperative binding of eukaryotic translation initiation factor (eIF) 3 and eIF4A to human eIF4G-1. J Biol Chem. 2000, 275: 41369–76.

[5] [5]
（英文）Lamphear, B.J.; et al. Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation. J Biol Chem. 1995, 270: 21975–83.

[6] [6]
（英文）Park, H.S.; et al. Eucaryotic initiation factor 4B controls eIF3-mediated ribosomal entry of viral reinitiation factor. Embo J. 2004, 23: 1381–91.

[7] [7]
（英文）Park, H.S.; et al. A plant viral "reinitiation" factor interacts with the host translational machinery. Cell. 2001, 106: 723–33.

[8] [8]
（英文）Dong, Z. and Zhang, J.T. Initiation factor eIF3 and regulation of mRNA translation, cell growth, and cancer. Crit Rev Oncol Hematol. 2006, 59: 169–80.

[9] [9]
（英文）Pyronnet, S. and Sonenberg, N. Cell-cycle-dependent translational control. Curr Opin Genet Dev. 2001, 11: 13–8.

[10] [10]
（英文）Shen, X.; et al. Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3. FEBS Lett. 2004, 573: 139–46.

[11] [11]
（英文）Phan, L.; et al. Identification of a translation initiation factor 3 (eIF3) core complex, conserved in yeast and mammals, that interacts with eIF5. Mol Cell Biol. 1998, 18 (8): 4935–46.

[12] [12]
（英文）Fraser, C.S.; et al. The j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro. J Biol Chem. 2004, 279 (10): 8946–56.

[13] [13]
（英文）Burks, E.A.; et al. Plant initiation factor 3 subunit composition resembles mammalian initiation factor 3 and has a novel subunit. J Biol Chem. 2001, 276 (3): 2122–31.

[14] [14]
（英文）Scheel, H. and Hofmann, K. Prediction of a common structural scaffold for proteasome lid, COP9-signalosome and eIF3 complexes. BMC Bioinformatics. 2005, 6 (1): 71.

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