scholarly journals Role of Hypusinated Eukaryotic Translation Initiation Factor 5A in Polyamine Depletion-induced Cytostasis

2007 ◽  
Vol 282 (48) ◽  
pp. 34700-34706 ◽  
Author(s):  
Mervi T. Hyvönen ◽  
Tuomo A. Keinänen ◽  
Marc Cerrada-Gimenez ◽  
Riitta Sinervirta ◽  
Nikolay Grigorenko ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation

scholarly journals The eukaryotic translation initiation factor eIF4E harnesses hyaluronan production to drive its malignant activity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Hiba Ahmad Zahreddine ◽  
Biljana Culjkovic-Kraljacic ◽  
Audrey Emond ◽  
Filippa Pettersson ◽  
Ronald Midura ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Glucuronic Acid ◽  
Building Blocks ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Hyaluronic Acid Synthase ◽  
Eukaryotic Translation Initiation

The microenvironment provides a functional substratum supporting tumour growth. Hyaluronan (HA) is a major component of this structure. While the role of HA in malignancy is well-defined, the mechanisms driving its biosynthesis in cancer are poorly understood. We show that the eukaryotic translation initiation factor eIF4E, an oncoprotein, drives HA biosynthesis. eIF4E stimulates production of enzymes that synthesize the building blocks of HA, UDP-Glucuronic acid and UDP-N-Acetyl-Glucosamine, as well as hyaluronic acid synthase which forms the disaccharide chain. Strikingly, eIF4E inhibition alone repressed HA levels as effectively as directly targeting HA with hyaluronidase. Unusually, HA was retained on the surface of high-eIF4E cells, rather than being extruded into the extracellular space. Surface-associated HA was required for eIF4E’s oncogenic activities suggesting that eIF4E potentiates an oncogenic HA program. These studies provide unique insights into the mechanisms driving HA production and demonstrate that an oncoprotein can co-opt HA biosynthesis to drive malignancy.

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