Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs.
Eukaryotic initiation factor (eIF) 4E, the mRNA 5'-cap-binding protein, mediates the association of eIF4F with the mRNA 5'-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported to the nucleus via its interaction with 4E-T (4E-transporter), but it is unclear how it is retained in the nucleus. Here we show that a sizable fraction (approximately 30%) of 4E-BP1 is localized to the nucleus, where it binds eIF4E. In mouse embryo fibroblasts (MEFs) subjected to serum starvation and/or rapamycin treatment, nuclear 4E-BPs sequester eIF4E in the nucleus. A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras-expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization.
Department of Biochemistry, McGill University, Montréal, Québec H3G 1Y6, Canada.
Liwei
L
Rong
Mark
M
Livingstone
Rami
R
Sukarieh
Emmanuel
E
Petroulakis
Anne-Claude
AC
Gingras
Katherine
K
Crosby
Bradley
B
Smith
Roberto D
RD
Polakiewicz
Jerry
J
Pelletier
Maria A
MA
Ferraiuolo
Nahum
N
Sonenberg
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D039561:Eukaryotic Initiation Factor-4E / Q000032:analysis / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology; D051379:Mice; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins; D012333:RNA, Messenger