The Bad, the Good and eIF3e/INT6.
Recent research on translation and protein synthesis in several pathologies, including cancer, peripheral artery disease, and wound healing, demonstrates the key role played by translational factors in tumorigenic and angiogenic processes. This review will focus on one specific translational factor, eIF3e also called INT6, the "e" subunit of the translation initiation factor eIF3. INT6/eIF3e has recently been described as a multifunction protein playing a role in translation, protein degradation, DNA repair, nonsense-mediated mRNA decay, cell cycle and control of cell response to low oxygen (hypoxia or ischemia) through modulation of the Hypoxia Inducible Factors (HIFs). Interestingly, INT6/eIF3e is a double-edged sword that has both oncogenic and tumor suppressive abilities. In addition to its role in tumorigenesis, its silencing has recently been suggested as a potential therapeutic strategy to improve cell survival and function after ischemic injuries. Although a deeper understanding of the molecular mechanisms involved in these pathophysiological functions is essential, particularly to transform thein vitro/in vivofindings into clinical applications, INT6/eIF3e modulation could provide therapeutic benefit for a variety of human diseases such as cancer or vascular diseases.
INSERM U1037, Centre de Recherche en Cancerologie de Toulouse, 2 Avenue Hubert Curien, Toulouse 31100, France.
Julie
J
Sesen
Johns Hopkins University, Department of Neurosurgery, Hunterian Brain Tumor Laboratory, 15550 Orleans Street, Baltimore, Maryland 21231.
Joshua
J
Casaos
Johns Hopkins University, Department of Neurosurgery, Hunterian Brain Tumor Laboratory, 15550 Orleans Street, Baltimore, Maryland 21231.
Sarah J
SJ
Scotland
INSERM U1037, Centre de Recherche en Cancerologie de Toulouse, 2 Avenue Hubert Curien, Toulouse 31100, France.
Cathy
C
Seva
Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104.
T S Karin
TS
Eisinger-Mathason
INSERM U1037, Centre de Recherche en Cancerologie de Toulouse, 2 Avenue Hubert Curien, Toulouse 31100, France, nicolas.skuli@inserm.fr.
Nicolas
N
Skuli
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D009857:Oncogenes; D021122:Protein Subunits
D051792:Basic Helix-Loop-Helix Proteins; D039621:Eukaryotic Initiation Factor-3; D021122:Protein Subunits