Eukaryotic Translation Initiation Factor 3F (eIF3f) is a subunit of the eukaryotic translation initiation factor 3 (eIF3) complex, which plays a crucial role in the initiation phase of protein synthesis in eukaryotic cells. This complex is essential for both cap-dependent and cap-independent translation initiation, facilitating the assembly of the 43S pre-initiation complex (PIC) and the recruitment of other initiation factors .
eIF3f is a multifunctional protein that interacts with various proteins involved in cellular processes such as protein synthesis, DNA repair, and viral mRNA editing . It is a component of the eIF3 complex, which associates with the 40S ribosome and aids in the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi, and eIF-5 to form the 43S PIC . This complex is essential for the proper positioning of ribosomes at the mRNA start codon, ensuring accurate translation initiation .
eIF3f has been implicated in several critical cellular processes. It exhibits deubiquitinase activity, which is essential for regulating the activation of the Notch signaling pathway . The Notch pathway is highly conserved and plays a vital role in development, with its misregulation linked to various diseases. eIF3f’s deubiquitinase activity targets the activated Notch receptor, preventing its monoubiquitination and facilitating its processing by gamma-secretase .
In addition to its role in translation initiation and Notch signaling, eIF3f is involved in cell cycle regulation and proliferation. Its deregulation can compromise cell viability, highlighting its importance in maintaining cellular homeostasis .
Mutations or alterations in the expression of eIF3f have been associated with several diseases. For instance, eIF3f has been implicated in intellectual developmental disorders and neurodevelopmental disorders with dysmorphic facies and distal limb anomalies . Understanding the function and regulation of eIF3f can provide insights into the molecular mechanisms underlying these conditions and potentially lead to the development of targeted therapies.