Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E.

Haghighat, Ashkan; Mader, Sylvie; Pause, Arnim; Sonenberg, Nahum

doi:10.1002/j.1460-2075.1995.tb00257.x

Cited by 559 publications

(484 citation statements)

References 55 publications

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“…When phosphorylated by mTOR, 4E-BP1 releases eIF4E. This allows eIF4E to bind eIF4G and stimulates the translation of 5 0 capped mRNAs (Haghighat et al, 1995). Given the activation of mTOR after TBI, we determined if 4E-BP1 phosphorylation was also altered after TBI.…”

Section: Mtor Signaling After Traumatic Brain Injury S Chen Et Almentioning

confidence: 99%

Alterations in Mammalian Target of Rapamycin Signaling Pathways after Traumatic Brain Injury

Chen

Atkins

Liu

et al. 2006

J Cereb Blood Flow Metab

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In response to traumatic brain injury (TBI), neurons initiate neuroplastic processes through the activation of intracellular signaling pathways. However, the molecular mechanisms underlying neuroplasticity after TBI are poorly understood. To study this, we utilized the fluid-percussion brain injury (FPI) model to investigate alterations in the mammalian target of rapamycin (mTOR) signaling pathways in response to TBI. Mammalian target of rapamycin stimulates mRNA translation through phosphorylation of eukaryotic initiation factor 4E binding protein-1 (4E-BP1), p70 ribosomal S6 kinase (p70S6K), and ribosomal protein S6 (rpS6). These pathways coordinate cell growth and neuroplasticity via dendritic protein synthesis. Rats received sham surgery or moderate parasagittal FPI on the right side of the parietal cortex, followed by 15 mins, 30 mins, 4 h, 24 h, or 72 h of recovery. Using Western blot analysis, we found that mTOR, p70S6K, rpS6, and 4E-BP1 phosphorylation levels were significantly increased in the ipsilateral parietal cortex and hippocampus from 30 mins to 24 h after TBI, whereas total protein levels were unchanged. Using confocal microscopy to localize these changes, we found that rpS6 phosphorylation was increased in the parietal cortex and all subregions of the hippocampus. In accordance with these results, eIF4E, a key, rate-limiting mRNA translation factor, was also phosphorylated by mitogen-activated protein kinase-interacting kinase 1 (Mnk1) 15 mins after TBI. Together, these results suggest that changes in mRNA translation may be one mechanism that neurons use to respond to trauma and may contribute to the neuroplastic changes observed after TBI.

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Section: Mtor Signaling After Traumatic Brain Injury S Chen Et Almentioning

confidence: 99%

Alterations in Mammalian Target of Rapamycin Signaling Pathways after Traumatic Brain Injury

Chen

Atkins

Liu

et al. 2006

J Cereb Blood Flow Metab

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show abstract

“…However this interaction is inhibited by a small family of 4E binding proteins (4E-BPs) which can compete with eIF4G for binding to eIF4E Haghighat et al, 1995;Altmann et al, 1997;Matsuo et al, 1997). The extent of complex formation between the best studied of these proteins, 4E-BP1 (also known as PHAS-I) (Lawrence and , and eIF4E is regulated by the phosphorylation of 4E-BP1 (Graves et al, 1995;Von Manteu el et al, 1996;Brunn et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

1998

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We have investigated the e ect of inducing apoptosis in BJAB and Jurkat cells on the cellular content of several polypeptide chain initiation factors. Serum deprivation results in inhibition of protein synthesis and induction of apoptosis in BJAB cells; at early times, there is selective degradation of polypeptide initiation factor eIF4G but no major losses of other key initiation factors. The disappearance of full length eIF4G is accompanied by the appearance of smaller forms of the protein, including a major product of approximately 76 kDa. Apoptosis induced by cycloheximide results in similar e ects. Both total cytoplasmic eIF4G and eIF4G associated with eIF4E are degraded with a half-life of 2 ± 4 h under these conditions. Treatment of serum-starved or cycloheximide-treated cells with Z-VAD.FMK or Z-DEVD.FMK, which inhibit caspases required for apoptosis, protects eIF4G from degradation and blocks the appearance of the ca. 76 kDa product. Exposure of BJAB cells to rapamycin rapidly inhibits protein synthesis but does not lead to acute degradation of eIF4G. In both BJAB and Jurkat cells induction of apoptosis with anti-Fas antibody or etoposide also results in the selective loss of eIF4G, which is inhibitable by Z-VAD.FMK. These data suggest that eIF4G is selectively targeted for cleavage as cells undergo apoptosis and is a substrate for proteases activated during this process.

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“…This occurs through modulation of the amount of eIF4E present within the cell or, more often, through regulation of the association of eIF4E with a family of three translational repressors, the eIF4E-binding proteins (4E-BPs) (32). The 4E-BPs do not inhibit eIF4E binding to the cap but, instead, block eIF4F assembly by competing with eIF4Gs for a common binding site on eIF4E (11,23). The binding of eIF4E to 4E-BPs is regulated through phosphorylation of 4E-BPs, as hyperphosphorylation of 4E-BP1 inhibits the association of 4E-BPs with eIF4E (10,20,45).…”

mentioning

confidence: 99%

Selective Modification of Eukaryotic Initiation Factor 4F (eIF4F) at the Onset of Cell Differentiation: Recruitment of eIF4GII and Long-Lasting Phosphorylation of eIF4E

Caron

Charon

Cramer

et al. 2004

Molecular and Cellular Biology

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mRNA translation is mainly regulated at the level of initiation, a process that involves the synergistic action of the 5 cap structure and the 3 poly(A) tail at the ends of eukaryotic mRNA. The eukaryote initiation factor 4G(eIF4G) is a pivotal scaffold protein that forms a critical link between mRNA cap structure, poly(A) tail, and the small ribosomal subunit. There are two functional homologs of eIF4G in mammals, the original eIF4G, renamed eIF4GI, and eIF4GII that functionally complements eIF4GI. To date, biochemical and functional analysis have not identified differential activities for eIF4GI and eIF4GII. In this report, we demonstrate that eIF4GII, but not eIF4GI, is selectively recruited to capped mRNA at the onset of cell differentiation. This recruitment is coincident with a strong and long-lasting phosphorylation of eIF4E and the release of 4E-BP1, a suppressor of eIF4E function, from the cap structure, without a concomitant change in 4E-BP1's phosphorylation. Our data further indicate that cytokines such as thrombopoietin can differentially regulate eIF4GI/II activities. These results provide the first evidence that eIF4GI/II does fulfill selective roles in mammalian cells.

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Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E.

Cited by 559 publications

References 55 publications

Alterations in Mammalian Target of Rapamycin Signaling Pathways after Traumatic Brain Injury

Alterations in Mammalian Target of Rapamycin Signaling Pathways after Traumatic Brain Injury

Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

Selective Modification of Eukaryotic Initiation Factor 4F (eIF4F) at the Onset of Cell Differentiation: Recruitment of eIF4GII and Long-Lasting Phosphorylation of eIF4E

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