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Eukaryotic initiation factor

There exist many more eukaryotic initiation factors (eIF) than prokaryotic initiation factors due to greater biological complexity. Processes eIF is involved in include: formation of initation complexes with 5' mRNA and complexing with Met-tRNAi, binding mRNA-factor to Met-tRNAi, scanning mRNA for the initiator codon AUG, locating the binding site of initator tRNA to the AUG start site, and joining of the 60S subunit to create the 80S subunit.

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



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. eIF4A - an RNA helicase - is important for resolving any secondary structures the mRNA transcript may form. eIF4E binds the 5' cap of the mRNA and the rate-limiting step for cap-dependent translation.

eIF4B contains two RNA binding domains - one non-specific interacts with mRNA, while 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.

eIF1 & eIF 3

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 either by 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.


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.


eIF5 is a GTPase activating protein.

See also

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Eukaryotic_initiation_factor". A list of authors is available in Wikipedia.
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