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，在哺乳动物细胞中，其分子量超过了600KDa。eIF3是真核翻译起始进程中起着核心作用。^[1]例如，eIF3可以使eIF2·GTP·Met-tRNA_i三联体复合物稳定地结合到40S核糖体亚基上，并促使43S前起始复合物的形成；它能够通过促进mRNA与40S亚基结合；而且，它还可以与游离的40S亚基结合，影响40S亚基与60S亚基及其他eIF的结合或解离等等。^[2]

eIF3是一个结构中心，可以与不同的真核起始因子以及RNA结合来调控整个翻译起始进程。^[3]

eIF3是一个多亚基复合物，也是最复杂的起始因子。哺乳动物中存在13种不同的亚基（a、b、c、d、e、f、g、h、i、j、k、l和m），而部分酵母中只有6个（a、b、c、g、i、j）。^[3]^[2]

功能

eIF3参与了真核翻译起始进程中大多数的反应。^[1]eIF3可以与游离的40S核糖体亚基结合，阻止40S亚基与60S核糖体亚基的直接结合，从而防止形成无翻译活性的80S核糖体；通过与eIF2的相互作用，eIF3可以使eIF2·GTP·Met-tRNA_i三联体复合物稳定地结合到40S亚基上，并促使43S前起始复合物的形成；eIF3可能通过与eIF4G的相互作用^[4]^[5]来或者通过直接与mRNA结合，促进mRNA与40S亚基结合，从而帮助48S前起始复合物的形成。eIF3也在重起始（reinitiation）的扫描和起始AUG密码子的选择中发挥作用。^[6]^[7]

除了在翻译起始过程中发挥核心作用，eIF3还被发现参与翻译过程以及细胞周期的调控。^[8]^[9]通过调节不同类型的mRNA的翻译起始，eIF3就可能选择性地调控蛋白的合成，从而对细胞的生长进行调控。而eIF3的a、b、e和k^[10]亚基都可能参与细胞周期调控。

亚基组成和结构

eIF3是一个多亚基复合物，目前发现的亚基共有13个，但不同的物种所含的亚基数量差异很大，例如哺乳动物中含有所有的13个亚基，而酿酒酵母中只含有6个亚基。eIF3许多亚基中都含有PCI和MPN结构域，这两类结构域都是参与蛋白-蛋白相互作用的；而eIF3c和3g中出现的RNA识别（RNA recognition motif，RRM）结构域则可能是参与RNA的结合。这些结构域提示eIF3是一个结构中心，通过与不同的起始因子以及RNA结合来调控整个翻译起始进程。^[2]尽管在亚基数目上有很大区别，但在酵母和人中都发现a、b、c、g和i亚基能够形成一个核心复合物，这5个亚基的氨基酸序列相当保守，而且它们对于酵母的生长都是必需的，^[11]^[12]因此这5个亚基就被称为核心亚基，而其他亚基则被称为非核心亚基。

**eIF3亚基组成**^[3]^[13]
亚基	包含结构域	功能
a	PCI	与40S亚基和eIF4F结合；参与多因子复合物（MFC）聚合；参与招募三联体和mRNA
b	RRM	与40S亚基结合；参与MFC聚合、招募三联体和mRNA；参与扫描起始密码子
c	PCI	与40S亚基结合；参与MFC聚合、招募三联体和mRNA、AUG密码子识别
d	-	可能为mTOR和S6K1蛋白提供结合位点
e	PCI	与eIF4B和CaMV TAV（重起始中）结合
f	MPN	-
g	RRM、锌指	-
h	MPN	-
i	WD40	-
j	-	与40S亚基结合；参与MFC聚合
k^[14]	PCI	与40S亚基结合
l	-	-
m	PCI	-

参考资料

[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 (编). 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.

参见

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 (编). 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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