Increase in cap- and IRES-dependent protein synthesis by overproduction of translation initiation factor eIF4G.
The role of eIF4G during the initiation of protein synthesis was studied using mouse mammary carcinoma FM3A cells and FM4G cells that overproduce an N-terminally truncated form of eIF4G, which lacks the binding site of poly(A)-binding protein. An increase in eIF4G was correlated with an increase in protein synthesis and RNA helicase activity. Translation of mRNAshaving both short and long 5'-untranslated regions (5'-UTR) increased significantly in FM4G cells compared to that in FM3A cells. Both full-length and N-terminally truncated eIF4G transfectants of NIH3T3 cells formed colonies in soft agar and increased the saturation density of cell growth, indicating that both eIF4Gs function similarly. We also found that an internal ribosome entry site (IRES) exists in the 5'-UTR of ornithinedecarboxylase mRNA and that IRES-dependent protein synthesis increased in FM4G cells. Our results indicate that an increase in eIF4G contributes to the formation of active eIF4F similarly to that caused by an increase in eIF4E, as well as to a stimulation of IRES-dependent protein synthesis.
Hayashi
S
S
Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, 263-8522, Japan.
Nishimura
K
K
Fukuchi-Shimogori
T
T
Kashiwagi
K
K
Igarashi
K
K
D016475:3T3 Cells; D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009955:Ornithine Decarboxylase / Q000235:genetics; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D039102:Poly(A)-Binding Proteins; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism*; D020365:RNA Helicases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D020121:5' Untranslated Regions; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D010448:Peptide Initiation Factors; D039102:Poly(A)-Binding Proteins; D012315:RNA Caps; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D020365:RNA Helicases; D009955:Ornithine Decarboxylase