RRC ID 71997
Author Takahashi S, Shibutani S, Iwata H.
Title Nuclear-targeted 4E-BP1 is dephosphorylated, induces nuclear translocation of eIF4E, and alters mRNA translation.
Journal Exp Cell Res
Abstract Mechanistic target of rapamycin complex 1 (mTORC1) phosphorylates and inhibits eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). This leads to the release of eIF4E from 4E-BP1 and the initiation of eIF4E-dependent mRNA translation. In this study, we examined the expression of a 4E-BP1-based reporter (mTORC1 activity reporter; TORCAR) with various localization signal tags to clarify the relationship between the localization of 4E-BP1 and its phosphorylation. Phosphorylation of 4E-BP1 at threonine 37/46 and serine 65 was efficient at lysosomes and the plasma membrane, whereas it was significantly decreased in the nucleus. In addition, the localization of endogenous eIF4E shifted from the cytoplasm to the nucleus only when nuclear-localized TORCAR was expressed. Nuclear-localized TORCAR decreased cyclin D1 protein levels and altered cell cycle distribution. These data provide an experimental tool to manipulate the localization of endogenous eIF4E without affecting mTORC1 and highlight the important role of nuclear-cytoplasmic shuttling of eIF4E.
Volume 418(1)
Pages 113246
Published 2022-9-1
DOI 10.1016/j.yexcr.2022.113246
PII S0014-4827(22)00239-7
PMID 35697076
MeSH Cell Cycle Proteins / metabolism Eukaryotic Initiation Factor-4E* / genetics Eukaryotic Initiation Factor-4E* / metabolism Mechanistic Target of Rapamycin Complex 1 / genetics Mechanistic Target of Rapamycin Complex 1 / metabolism Phosphoproteins / genetics Phosphoproteins / metabolism Phosphorylation Protein Biosynthesis*
IF 3.383
Human and Animal Cells 293T(RCB2202)