This entry represents eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1). EIF4EBP1 is a repressor of translation that binds to EIF4E and prevents its assembly into the eIF4F complex. EIF4EBP1 has to be hypophosphorylated to bind to EIF4E; the hyperphosphorylated form dissociates from EIF4E []. The phosphorylation state of EIF4EBP1 is affected by hormones such as insulin []and is regulated by mTORC1 []. When eIF4E levels are low, hypophosphorylated EIF4EBP1 is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation, and translation is maintained [].
The late 100kDa protein (also known as L4) inhibits host translation while promoting late viral translation by ribosome shunting []. It blocks host cap-dependent translation by binding to eIF4G, displacing MKNK1 from cap initiation complexes and preventing EIF4E phosphorylation [].
This entry represents a group of eIF4E binding proteins, including eIF4E transporter (eIF4E-T) from mammals, cup protein from D. melanogaster and ifet-1 from C. elegans. Protein cup functions in Smaug-mediated translational repression [, ]. Ifet-1 is a broad-scale translational repressor in C. elegans [, ]. eIF4E-T is the transporter protein for shuttling the mRNA cap-binding protein eIF4E protein, targeting it for nuclear import. eIF4E-T contains several key binding domains including two functional leucine-rich NESs (nuclear export signals) between residues 438-447 and 613-638 in the human protein. The other two binding domains are an eIF4E-T-binding site, between residues 27-42 in , and a bipartite NLS (nuclear localisation signals) between 194-211, and these lie in family eIF4E-T_N. eIF4E-T is the eukaryotic translation initiation factor 4E that is the rate-limiting factor for cap-dependent translation initiation [].
This entry represents eIF4E-associated protein (Eap1) from yeast, which plays a role in cell growth and is implicated in the TOR signaling cascade. Eap1 binds to eIF4E and regulates translation. It competes with eIF4G (the large subunit of the cap-binding complex, eukaryotic initiation factor 4F (eIF4F)) for binding to eIF4E and accelerates mRNA degradation by promoting decapping [, , , ]. It associates with Puf5p and Dhh1p, being essential for Puf5p mediated repression []. This family also includes the uncharacterised protein from S. pombe SPCC14G10.04 () which has been shown to interact with eIF4E, 4F complex subunits [].
This family consists of several eukaryotic translation initiation factor 4E binding proteins (EIF4EBP1, -2 and -3). Translation initiation in eukaryotes is mediated by the cap structure (m7GpppN, where N is any nucleotide) present at the 5' end of all cellular mRNAs, except organellar. The cap is recognised by eukaryotic initiation factor 4F (eIF4F), which consists of three polypeptides, including eIF4E, the cap-binding protein subunit. The interaction of the cap with eIF4E facilitates the binding of the ribosome to the mRNA. eIF4E activity is regulated in part by translational repressors, 4E-BP1, 4E-BP2 and 4E-BP3 which bind to it and prevent its assembly into eIF4F [].
This entry represents eukaryotic translation initiation factor 4 gamma 3 (EIF4G3), a component of the eIF4F protein complex. The eIF4F complex varies according to the environment, but consists at least of EIF4A, EIF4E and EIF4G1/EIF4G3 []. The eIF4F complex is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome []. During viral infection, EIF4G3 may be cleaved to switch off host protein translation. Among the viral endopeptidases known to cleave EIF4G3 are: rhinovirus picornain 2A []and foot-and-mouth disease virus L-peptidase [].
This entry includes cytoplasmic fragile X messenger ribonucleoprotein 1-interacting proteins from humans and their homologues, such as Sra-1 (specifically Rac1-associated protein 1) from Drosophila and PIROGI from Arabidopsis. In humans, there are two members, CYFIP1 and CYFIP2. They both interact with FMRP (Fragile X messenger ribonucleoprotein 1), which is responsible for pathologic manifestations in the Fragile X Syndrome. CYFIP1 interacts with the small GTPase Rac1 [, ]. CYFIP1 represses cap-dependent translation of mRNA by interacting with the initiation factor eIF4E []. CYFIP1 and CYFIP2 are part of the Wiskott-Aldrich syndrome protein-family verprolin-homologous protein (WAVE) complex that regulates actin polymerization at synapses []. Drosophila Sra-1 interacts with the Kette and Wasp. It is required for neuronal and bristle development in Drosophila []. PIROGI is part of a WAVE complex that activates the ARP2/3 complex and is Involved in regulation of actin organization [].
