Tumor necrosis factor induces phosphorylation of a 28-kDa mRNA cap-binding protein in human cervical carcinoma cells.

Marino, Michael W.; Pfeffer, Lawrence M.; Guidon, Peter T.; Donner, David B.

doi:10.1073/pnas.86.21.8417

Cited by 50 publications

(24 citation statements)

References 28 publications

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“…eIF-4E contains one major site of phosphorylation at Ser-53 (10, 21); decreased phosphorylation of eIF-4E has been correlated with the decrease in protein synthesis during heat shock (4) and mitosis (2). Enhanced phosphorylation of eIF-4E has been observed in 3T3-L1 cells stimulated with phorbol esters and insulin (16,17) as well as in human cervical carcinoma cells treated with tumor necrosis factor a (15) and serum-stimulated Swiss 3T3 cells (11). Significantly, mutation of Ser-53 to alanine prevents the association of eIF-4E with the 48S initiation complex (10).…”

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confidence: 99%

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Phosphorylation of eukaryotic translation initiation factor 4E is increased in Src-transformed cell lines.

Frederickson¹,

Montine²,

Sonenberg³

1991

Mol. Cell. Biol.

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Eukaryotic initiation factor 4F (eIF-4F) is a three-subunit complex that binds the 5' cap structure (m7GpppX, where X is any nucleotide) of eukaryotic mRNAs. This factor facilitates ribosome binding by unwinding the secondary structure in the mRNA 5' noncoding region. The limiting component of the 4F complex is believed to be the 24-kDa cap-binding phosphoprotein, eIF-4E. In this report, we describe the phosphorylation of eIF-4E in response to expression of the tyrosine kinase oncoproteins pp6vs-c and pp60c-src527F' The results suggest that eIF-4E functions as a downstream target of the phosphorylation cascade induced by tyrosine-specific protein kinases as well as by effectors of the mitogenic response.

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confidence: 99%

“…Furthermore, mixing of these phosphopeptides prior to electrophoresis and chromatography ( Fig. 4G and H (11,(15)(16)(17). To Fig.…”

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confidence: 99%

Phosphorylation of eukaryotic translation initiation factor 4E is increased in Src-transformed cell lines.

Frederickson¹,

Montine²,

Sonenberg³

1991

Mol. Cell. Biol.

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“…Moreover, the biochemical (Joshi-Barve et al 1990) and biological (Morley et al 1991) activities of eIF-4E depend on its state of phosphorylation on Ser-53 (Rychlik et al 1987). Phosphorylation of eIF-4E is increased in response to mitogens, growth factors, and the transforming src and ras genes, suggesting that eIF-4E is an important component of various mitogenic signaling pathways (Marino et al 1989;Morley and Traugh 1989;Kaspar et al 1990;Frederickson et al 1991Rinker-Schaeffer et al 1992).…”

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confidence: 99%

Ras mediates translation initiation factor 4E-induced malignant transformation.

Smith²,

et al. 1992

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Translation initiation factor eIF-4E binds to the eukaryotic mRNA 5' cap structure (m7GpppN, where N is any nucleotide), eIF-4E is a limiting factor in translation and plays a key role in regulation of translation. We have shown previously that overexpression of eIF-4E in rodent fibroblasts results in tumorigenic transformation. eIF-4E also exhibits mitogenic activity when microinjected into serum-starved NIH-3T3 cells. To understand the mechanisms by which eIF-4E exerts its mitogenic property, we examined the involvement of the Ras signaling pathway in this activity. Here, we report that Ras is activated in eIF-4E-overexpressing cells, as the proportion of GTP-bound Ras is increased. Overexpression of the negative effector of cellular Ras, GTPase activating protein, causes reversion of the transformed phenotype. Furthermore, we show that neutralizing antibodies to Ras, or a dominant-negative mutant of Ras, inhibit the mitogenic activity of eIF-4E. We conclude that eIF-4E exerts its mitogenic and oncogenic activities by the activation of Ras.

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“…The state of eIF-4E phosphorylation correlates directly with its activity (45). Decreased phosphorylation of eIF-4E is accompanied by a reduction in protein synthesis during heat shock (14) and mitosis (2), while enhanced phosphorylation has been observed in a variety of cell lines treated with growth-promoting agents (6,13,18,37,43,46) and in response to expression of tyrosine kinase oncogenes, such as src (18) or Ick (20). Mutation of Ser-53 to an Ala residue prevents the association of eIF-4E with the 48S initiation complex (35) and blocks the ability of overexpressed eIF-4E to transform fibroblast cells in culture (39), highlighting the importance of phosphorylation of Ser-53 for control of cell growth.…”

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Phosphorylation of translation initiation factor eIF-4E is induced in a ras-dependent manner during nerve growth factor-mediated PC12 cell differentiation.

1992

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Translation initiation factor eIF-4E, which binds to the 5' cap structure of eukaryotic mRNAs, is believed to play an important role in the control of cell growth. Consistent with this, overexpression of eIF4E in fibroblasts results in their malignant transformation. The activity of eIF-4E is thought to be regulated by phosphorylation on a single serine residue (Ser-53). Treatment of rat pheochromocytoma (PC12) cells with nerve growth factor (NGF) strongly curtails their growth and causes their differentiation into cells that resemble sympatheticneurons. The present study shows that eIF-4E is rapidly phosphorylated in PC12 cells upon NGF treatment, resulting in a significant increase in the steady-state levels of the phosphorylated protein. In contrast, epidermal growth factor, a factor which elicits a weak mitogenic response in PC12 cells, did not significantly enhance eIF-4E phosphorylation. We also show that although the mitogen and tumor promoter, phorbol 12-myristate-13-acetate, is able to induce phosphorylation of eIF-4E in PC12 cells, the NGF-mediated increase is primarily a protein kinase C-independent response. The NGF-induced enhancement of eiF4E phosphorylation is abrogated in PC12 cells expressing a dominant inhibitory ras mutant (Ser-17 replaced by Asn), indicating that eIF-4E phosphorylation is dependent on a ras signalling pathway. As phosphorylation of eIF-4E effects translation initiation, these results suggest that NGF-mediated and ras-dependent eIF-4E phosphorylation may play a role in switching the pattern of gene expression during the differentiation of PC12 cells.Changes in translation rates play a significant role in the control of cell growth (for a recent review, see reference 31). Enhanced protein synthesis is obligatory for entry into and progression through the cell cycle (4, 5). Modulation of the rate of protein synthesis also occurs during heat shock (14, 51) and mitosis (17) and in response to cell growth modulators (60,63). These changes are effected primarily at the level of initiation, which is rate-limiting under most circumstances (34), and are thought to be governed by the phosphorylation state of key initiation factors (for a review, see reference 30).

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Tumor necrosis factor induces phosphorylation of a 28-kDa mRNA cap-binding protein in human cervical carcinoma cells.

Cited by 50 publications

References 28 publications

Phosphorylation of eukaryotic translation initiation factor 4E is increased in Src-transformed cell lines.

Phosphorylation of eukaryotic translation initiation factor 4E is increased in Src-transformed cell lines.

Ras mediates translation initiation factor 4E-induced malignant transformation.

Phosphorylation of translation initiation factor eIF-4E is induced in a ras-dependent manner during nerve growth factor-mediated PC12 cell differentiation.

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