Localisation and regulation of the eIF4E‐binding protein 4E‐BP3

Kleijn, Miranda; Scheper, Gert C.; Wilson, Mary L.; Tee, Andrew R.; Proud, Christopher G.

doi:10.1016/s0014-5793(02)03694-3

Cited by 21 publications

(17 citation statements)

References 21 publications

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“…Herein we provide evidence that a sizable fraction (z30%) of 4E-BP1 is present in the nucleus, contrary to earlier reports (Kim and Chen 2000;Kleijn et al 2002). The use of biochemical fractionation techniques suggested that 4E-BPs reside exclusively in the cytoplasm, but these techniques are subject to limitations due to leakage of small proteins from the nucleus.…”

Section: Discussioncontrasting

confidence: 83%

“…Biochemical fractionation experiments have previously led to the conclusion that 4E-BP1 localization is restricted to the cytoplasm (Kim and Chen 2000;Kleijn et al 2002;Zhang et al 2002). However, in these studies the possibility that 4E-BP1 leaked from the nucleus during the fractionation procedures due to its small molecular mass was not addressed.…”

Section: Introductionmentioning

confidence: 99%

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Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs

Liang

Livingstone²,

Sukarieh³

et al. 2008

RNA

114

112

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Eukaryotic initiation factor (eIF) 4E, the mRNA 59-cap-binding protein, mediates the association of eIF4F with the mRNA 59-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 (;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.

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Section: Discussioncontrasting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs

Liang

Livingstone²,

Sukarieh³

et al. 2008

RNA

114

112

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“…What could be the function of the nuclear Mnk2b? Although eIF4E has been found in the nuclear compartments of various cell types, we have consistently found that only a very small amount of eIF4E, if any, is present in the nucleus in HEK293 cells (16). Similarly, eIF4G is almost completely cytoplasmic in HEK293 cells (data not shown).…”

Section: Mnk2a and Mnk2b Localize Differentlymentioning

confidence: 61%

The N and C Termini of the Splice Variants of the Human Mitogen-Activated Protein Kinase-Interacting Kinase Mnk2 Determine Activity and Localization

Scheper¹,

Parra²,

Wilson³

et al. 2003

Molecular and Cellular Biology

136

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The cap-binding eukaryotic initiation factor eIF4E is phosphorylated by the mitogen-activated protein (MAP) kinase-interacting kinases (Mnk's). Three forms of the Mnk's exist in human cells: Mnk1, Mnk2a, and Mnk2b. These last two are derived from the same gene by alternative splicing and differ only at their C termini. While Mnk2a contains a MAP kinase-binding site in this region, Mnk2b lacks such a sequence and is much less readily activated by MAP kinases in vitro. Expression of Mnk2b in mammalian cells leads to increased phosphorylation of eIF4E, showing that it acts as an eIF4E kinase in vivo. While Mnk2a is cytoplasmic, a substantial amount of Mnk2b is found in the nucleus. Both enzymes contain a stretch of basic residues in their N termini that plays a role in binding to eIF4G and functions as a nuclear localization signal. Binding of eIF4G or nuclear import appears to be regulated by the C terminus of Mnk2a. Furthermore, the MAP kinase-binding site of Mnk2a regulates nuclear entry. Within the nucleus, Mnk2b and certain variants of Mnk2a that are present in the nucleus colocalize with the promyelocytic leukemia protein PML, which also binds to eIF4E.

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“…Whereas 4E-BP1 is mainly cytoplasmic, 4E-BP3 is also found in the nucleus (Kleijn et al, 2002). It shares this property with its partner, eIF4E, although the biological significance of this is unclear.…”

Section: Control Of the 4e-bps By Mtormentioning

confidence: 99%