Eukaryotic translation initiation factor 6, also known as Integrin beta 4binding protein, is a human gene. Hemidesmosomes are structures which link the basal lamina to the intermediate filamentcytoskeleton. An important functional component of hemidesmosomes is the integrin beta-4 subunit, a protein containing two fibronectin type III domains. The protein encoded by this gene binds to the fibronectin type III domains of ITGB4 and may help link ITGB4 to the intermediate filament cytoskeleton. The encoded protein, which is insoluble and found both in the nucleus and in the cytoplasm, can function as a translation initiation factor and catalyzes the association of the 40S and 60Sribosomal subunits along with eIF5 bound to GTP. Multiple transcript variants encoding several different isoforms have been found for this gene. EIF6 plays important roles in Eukaryotic 80S ribosomeformation, cell growth and gene expression. The 80Sribosome, which can separate into 40S and 60S subunits. EIF6 helps to protect mature 60s subunit and then EIF6 should disassociate with 60s subunit so that it can binds to 40s subunit to form ribosome. Keeping in balance of EIF6 is essential for the body: few EIF6 helps synthesis of normal ribosome, while large amount of EIF6 inhibited 60s subunits bind to 40s subunits.
Function
EIF6 exists both in nucleolus and cytoplasm. In the eukaryotic nucleolus, a 90S pre-ribosomal complex separate to a 60S pre-ribosomal complex and a 40S pre-ribosomal complex, which are involved in synthesis of mature ribosome. EIF6 is indispensable in 60S subunit biogenesis and deletion of EIF6 has lethal effect. The partial deletion of eIF6 results in decreasing of free 60S ribosomal subunit, which means it knocks the 40S/60S subunit ratio off balance, and limiting the speed of protein synthesis. 60S pre-ribosomal complex associated with eIF6 shuttle from nucleolus to cytoplasm and then eIF6 disassociated with pre-60S so that 60S subunit can binds to 40S subunit and continues to subsequent prograss. EIF6 can act as a rate-limiting translational initiation factor, and its expression levels influence the translational rate. Few of eIF6 will small accelerate protein translation, while large of eIF6 will block translational process by inhibiting production of ribosome. The activity of eIF6 also cause glycolysis and fatty acid synthesis by mRNAs' translational controlling.
Expression
EIF6 has different level of expression in different tissue and cell. EIF6 has high level of expression in stem cells and cycling cells, while it doesn't in postmitotic cells; high level in brain and epithelia, while low level in muscle.
Interactions
EIF6 has been shown to interact with FHL2, ITGB4 and GNB2L1. EIF6 plays important roles in 80S ribosome formation, cell growth and gene expression.
