Sumoylation of eIF4E activates mRNA translation.
Eukaryotic translation initiation factor 4E (eIF4E) is the cap-binding protein that binds the 5' cap structure of cellular messenger RNAs (mRNAs). Despite the obligatory role of eIF4E in cap-dependent mRNA translation, how the translation activity of eIF4E is controlled remains largely undefined. Here, we report that mammalian eIF4E is regulated by SUMO1 (small ubiquitin-related modifier 1) conjugation. eIF4E sumoylation promotes the formation of the active eIF4F translation initiation complex and induces the translation of a subset of proteins that are essential for cell proliferation and preventing apoptosis. Furthermore, disruption of eIF4E sumoylation inhibits eIF4E-dependent protein translation and abrogates the oncogenic and antiapoptotic functions associated with eIF4E. These data indicate that sumoylation is a new fundamental regulatory mechanism of protein synthesis. Our findings suggest further that eIF4E sumoylation might be important in promoting human cancers.
Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Suite 2.42D, Pittsburgh, Pennsylvania 15213, USA.
Xiang
X
Xu
Jaya
J
Vatsyayan
Chenxi
C
Gao
Christopher J
CJ
Bakkenist
Jing
J
Hu
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D014176:Protein Biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D025842:SUMO-1 Protein / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
D039561:Eukaryotic Initiation Factor-4E; D012333:RNA, Messenger; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins