EIF6
Description
The EIF6 (eukaryotic translation initiation factor 6) is a protein-coding gene located on chromosome 20.
EIF6, also known as Integrin beta 4 binding protein (ITGB4BP), is a human gene. Hemidesmosomes, structures linking the basal lamina to the intermediate filament cytoskeleton, contain the integrin beta-4 subunit (ITGB4), a protein with two fibronectin type III domains. EIF6 binds to these domains and may help link ITGB4 to the intermediate filament cytoskeleton. The protein encoded by this gene is insoluble, found both in the nucleus and cytoplasm, and functions as a translation initiation factor by catalyzing the association of the 40S and 60S ribosomal subunits along with eIF5 bound to GTP. Multiple transcript variants encoding several isoforms have been found for this gene. EIF6 plays crucial roles in eukaryotic 80S ribosome formation, cell growth, and gene expression. The 80S ribosome can separate into 40S and 60S subunits. EIF6 protects mature 60s subunits, then dissociates to allow binding to 40s subunits and ribosome formation. Maintaining the balance of EIF6 is essential: low levels promote normal ribosome synthesis, while high levels inhibit 60S subunit binding to 40S subunits. EIF6 exists in both the nucleolus and cytoplasm.
EIF6 binds to the 60S ribosomal subunit, preventing its association with the 40S subunit and formation of the 80S initiation complex in the cytoplasm. It acts as a stimulatory translation initiation factor downstream of insulin and growth factors. EIF6 also participates in ribosome biogenesis, associating with pre-60S subunits in the nucleus and facilitating their nuclear export. The release of EIF6 from 60S subunits in the cytoplasm and its nuclear relocalization are promoted by RACK1-dependent protein kinase C activity. In insulin-responsive tissues, EIF6 regulates fatty acid synthesis and glycolysis by controlling the translation of adipogenic transcription factors such as CEBPB, CEBPD, and ATF4, which contain G/C-rich or uORF sequences in their 5'UTRs. EIF6 is essential for ROS-dependent megakaryocyte maturation and platelet formation, regulating the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis. EIF6 participates in miRNA-mediated gene silencing via the RNA-induced silencing complex (RISC), playing a role in both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC. It modulates cell cycle progression and global translation in pre-B cells, with its activation appearing to be rate-limiting in tumorigenesis and tumor growth.
EIF6 is also known as CAB, EIF3A, ITGB4BP, b(2)gcn, eIF-6, p27(BBP), p27BBP.
