eIF3: a factor for human health and disease

Abstract

The eukaryotic initiation factor 3 (eIF3) is one of the most complex translation initiation factors in mammalian cells, consisting of several subunits (eIF3a to eIF3m). It is crucial in translation initiation and termination, and in ribosomal recycling. Accordingly, deregulated eIF3 expression is associated with different pathological conditions, including cancer. In this manuscript, we discuss the interactome and function of each subunit of the human eIF3 complex. Furthermore, we review how altered levels of eIF3 subunits correlate with neurodegenerative disorders and cancer onset and development; in addition, we evaluate how such misregulation may also trigger infection cascades. A deep understanding of the molecular mechanisms underlying eIF3 role in human disease is essential to develop new eIF3-targeted therapeutic approaches and thus, overcome such conditions.

Keywords: Cancer; eIF3; infection; neurodegenerative disease; translation; translation initiation factor; translational control.

Figure 1.

The mammalian eIF3 complex. eIF3 complex is composed of a PCI (Proteasome, COP9, eIF3)/MPN (Mpr1–Pad1 N-terminal) octamer including PCI subunits a, c, e, l, k and m (green) orientated sequentially to form an arc and MPN subunits f and h (yellow) connected with the former through f:m interaction; the b-i-g subunits module (red) is attached to the PCI/MPN octamer by its association with eIF3a carboxy-terminal domain (CTD); the two more peripheral positions are occupied by d and j subunits (blue), respectively.