Eukaryotic initiation factor 3
Eukaryotic initiation factor 3 (eIF3) is a
Function
eIF3 stimulates nearly all steps of translation initiation.
Interactions
eIF3 binds the
Several subunits of eIF3 contain
All five core subunits of budding yeast's eIF3 are present in heat-induced stress granules, along with several other translation factors.[10]
Structure
A functional eIF3 complex can be purified from native sources, or reconstituted from recombinantly expressed subunits.
Signaling
eIF3 serves as a hub for cellular signaling through S6K1 and mTOR/Raptor.[16] In particular, eIF3 is bound by S6K1 in its inactive state, and activated mTOR/Raptor binds to eIF3 and phosphorylates S6K1 to promote its release from eIF3. Phosphorylated S6K1 is then free to phosphorylate a number of its own targets, including eIF4B, thus serving as a mechanism of translational control.
Disease
Individual subunits of eIF3 are overexpressed (a, b, c, h, i, and m) and underexpressed (e, f) in multiple human cancers.[3] In breast cancer and malignant prostate cancer, eIF3h is overexpressed.[17] eIF3 has also been shown to bind a specific set of cell proliferation mRNAs and regulate their translation.[18] eIF3 also functions in the life cycles of a number of important human pathogens, including HIV and HCV. In particular, the d-subunit of eIF3 is a substrate of HIV protease, and genetic knockdown of eIF3 subunits d, e, or f results in increased viral infectivity for unknown reasons.[19]
Subunits
The eIF3 subunits exist at equal stoichiometry within the complex, with the exception of eIF3J, which is loosely bound and non-essential for viability in several species.[11][20][21] The subunits were originally organized alphabetically by molecular weight in mammals (A as the highest), but the arrangement of molecular weight can vary between species.[22]
Subunit | MW (kDa)[A] | Key Features |
---|---|---|
A | 167 | Upregulated in several human cancers.[3] Crosslinks directly to cellular mRNA.[18] Contains PCI domain.[12] |
B | 92 | Upregulated in several cancers.[3] Crosslinks directly to cellular mRNA.[18] Contains RRM.[11] |
C | 105 | Upregulated in several cancers.[3] Contains PCI domain.[12] Has a human paralog eIF3CL. |
D | 64 | Dispensable for growth in fission yeast.[4] Crosslinks directly to cellular mRNA[18] and binds the 5'cap of select mRNAs.[23] Substrate of HIV protease.[19] |
E | 52 | Downregulated in breast and lung cancers.[3] Nonessential for growth in fission yeast[24] and Neurospora crassa.[21] Contains PCI domain.[12] |
F | 38 | Downregulated in several cancers.[3] Contains MPN domain.[12] |
G | 36 | Contains RRM.[11] Crosslinks directly to cellular mRNA.[18] |
H | 40 | Upregulated in several cancers.[3] Nonessential for growth in fission yeast,[25] Neurospora crassa,[21] and human cell lines.[26][27] Contains MPN domain.[12] |
I | 36 | Upregulated in several cancers.[3] |
J | 29 | Loosely bound, non-stoichiometric subunit.[4] Binds the 40S ribosomal subunit within the decoding center.[28] Nonessential for growth in budding yeast.[4] |
K | 25 | Nonessential for growth in Neurospora crassa.[21] Contains PCI domain.[12] |
L | 67 | Nonessential for growth in Neurospora crassa.[21] Contains PCI domain.[12] |
M | 43 | Upregulated in human colon cancer.[3] |
A Molecular weight of human subunits from Uniprot.
See also
References
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