Target type: cellularcomponent
The eukaryotic translation initiation factor 4F complex is composed of eIF4E, eIF4A and eIF4G; it is involved in the recognition of the mRNA cap, ATP-dependent unwinding of the 5'-terminal secondary structure and recruitment of the mRNA to the ribosome. [GOC:hb, PMID:32883864, PMID:8449919]
The eukaryotic translation initiation factor 4F (eIF4F) complex is a crucial component of the translation initiation process in eukaryotes. This multi-protein complex plays a central role in recognizing and binding the 5' cap structure of messenger RNA (mRNA), facilitating its recruitment to the ribosome for protein synthesis. The eIF4F complex comprises three major subunits:
**eIF4E:** This subunit is the cap-binding protein. It binds directly to the 7-methylguanosine (m7G) cap at the 5' end of mRNA with high affinity, serving as the initial anchor for the mRNA to the ribosome.
**eIF4A:** This subunit is an ATP-dependent RNA helicase. Its primary function is to unwind secondary structures within the 5' untranslated region (5'UTR) of mRNA, facilitating the access of other components of the translation machinery to the initiation codon.
**eIF4G:** This subunit serves as a scaffolding protein, linking the other two subunits (eIF4E and eIF4A) together and bridging the interaction between eIF4F and other initiation factors, such as eIF3 and the 40S ribosomal subunit.
**Cellular Localization:** The eIF4F complex is primarily located in the cytoplasm, specifically in the vicinity of the ribosomes where translation takes place.
**Regulation:** The activity of the eIF4F complex is tightly regulated by various mechanisms, including phosphorylation, protein-protein interactions, and the availability of its subunits. These regulatory processes ensure that translation initiation is responsive to cellular cues and environmental changes.
**Function in Translation Initiation:** The eIF4F complex plays a critical role in the initiation of translation by:
1. **Recognizing and binding to the 5' cap of mRNA:** This interaction is essential for the recruitment of mRNA to the ribosome.
2. **Unwinding secondary structures within the 5'UTR:** This allows the ribosome to scan the mRNA for the initiation codon (AUG).
3. **Recruiting other initiation factors and the 40S ribosomal subunit:** The eIF4G subunit bridges the interaction between eIF4F and other components of the translation machinery, promoting the formation of the initiation complex.
**Clinical Significance:** Dysregulation of the eIF4F complex has been implicated in various diseases, including cancer, viral infections, and neurodegenerative disorders. Understanding the complex functions of eIF4F is crucial for developing novel therapeutic strategies targeting translation initiation pathways.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Eukaryotic initiation factor 4A-II | A eukaryotic initiation factor 4A-II that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Eukaryotic initiation factor 4A-I | A eukaryotic initiation factor 4A-I that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Eukaryotic translation initiation factor 4E | A eukaryotic translation initiation factor 4E that is encoded in the genome of human. [PRO:DNx, UniProtKB:P06730] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| cycloheximide | cycloheximide : A dicarboximide that is 4-(2-hydroxyethyl)piperidine-2,6-dione in which one of the hydrogens attached to the carbon bearing the hydroxy group is replaced by a 3,5-dimethyl-2-oxocyclohexyl group. It is an antibiotic produced by the bacterium Streptomyces griseus. Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. | antibiotic fungicide; cyclic ketone; dicarboximide; piperidine antibiotic; piperidones; secondary alcohol | anticoronaviral agent; bacterial metabolite; ferroptosis inhibitor; neuroprotective agent; protein synthesis inhibitor |
| rocaglamide | rocaglamide : An organic heterotricyclic compound that is 2,3,3a,8b-tetrahydro-1H-benzo[b]cyclopenta[d]furan substituted by hydroxy groups at positions 1 and 8b, methoxy groups at positions 6 and 8, a 4-methoxyphenyl group at position 3a, a phenyl group at position 3 and a N,N-dimethylcarbamoyl group at position 1. Isolated from Aglaia odorata and Aglaia duperreana, it exhibits antineoplastic activity. rocaglamide: RN refers to (1alpha,2alpha,3beta,3abeta,8bbeta)-isomer; isolated from stems of Aglaia elliptifolia; structure given in first source | monocarboxylic acid amide; monomethoxybenzene; organic heterotricyclic compound | antileishmanial agent; antineoplastic agent; metabolite |
| aglafoline | aglafolin : A heterotricyclic compound based on a 2,3,3a,8b-tetrahydro-1H-benzo[b]cyclopenta[d]furan framework substituted by hydroxy groups at positions C-1 and C-8b, a methoxycarbonyl group at C-2, a phenyl group at C-3, a 4-methoxyphenyl group at C-3a and methoxy groups at C-6 and C-8. A platelet aggregation inhibitor found in Aglaia elliptifolia and Aglaia odorata. aglafoline: a platelet activating factor antagonist; structure given in first source; isolated from Aglaia elliptifolia | methyl ester; organic heterotricyclic compound | metabolite; platelet aggregation inhibitor |
| sirolimus | sirolimus : A macrolide lactam isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent. Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. | antibiotic antifungal drug; cyclic acetal; cyclic ketone; ether; macrolide lactam; organic heterotricyclic compound; secondary alcohol | antibacterial drug; anticoronaviral agent; antineoplastic agent; bacterial metabolite; geroprotector; immunosuppressive agent; mTOR inhibitor |
| 6-mercapto-7-methylguanosine | 6-mercapto-7-methylguanosine: structure given in first source | ||
| hippuristanol | hippuristanol: from the gorgonian Isis hippuris | ||
| cgp 57380 | CGP 57380: inhibits the mitogen-activated protein kinase-interacting kinase Mnk1 | pyrazolopyrimidine | |
| silvestrol | silvestrol : An organic heterotricyclic compound that consists of a 2,3,3a,8b-tetrahydro-H-benzo[b]cyclopenta[d]furan framework substituted by hydroxy groups at positions C-1 and C-8b, a methoxycarbonyl group at C-2, a phenyl group at C-3, a 4-methoxyphenyl group at C-3a, a methoxy group at C-8 and a 1,4-dioxan-2-yloxy group at position C-6 which in turn is substituted by a methoxy group at position 3 and a 1,2-dihydroxyethyl group at position 6. Isolated from Aglaia silvestris, it exhibits antineoplastic activity. silvestrol: isolated from the fruit and twig of Aglaia silvestris | dioxanes; ether; methyl ester; organic heterotricyclic compound | antineoplastic agent; metabolite |
| 7-methyl-GTP | guanosine 5'-phosphate |