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.
Xu
Xiang
X
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.
Vatsyayan
Jaya
J
Gao
Chenxi
C
Bakkenist
Christopher J
CJ
Hu
Jing
J
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