Phosphorylation of the proto-oncogene product eukaryotic initiation factor 4E is a common cellular response to tumor necrosis factor.

Marino, Michael W.; Feld, Lea; Jaffe, Eric; Pfeffer, Lawrence M.; Han, Hyung-Mee; Donner, David B.

doi:10.1016/s0021-9258(18)49896-1

Cited by 33 publications

(1 citation statement)

References 28 publications

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“…Consistent with this, the phosphorylation state of eIF-4E in a cell is proportional to its proliferative state. Stimulation of cell growth by serum, tumor necrosis factor a, platelet-derived growth factor, and insulin results in enhanced phosphorylation of eIF-4E (7,8,19,23). Similarly, cells transformed by oncogenes contain a higher proportion of phosphorylated eIF-4E than do normal cells (7).…”

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The mRNA 5' Cap-Binding Protein, eIF-4E, Cooperates with v-myc or E1A in the Transformation of Primary Rodent Fibroblasts

Lazaris-Karatzas

Sonenberg

1992

Molecular and Cellular Biology

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We present evidence that eIF-4E, the mRNA 5' cap-binding protein, cooperates with two immortalizing oncogenes, v-myc and E1A, to cause transformation of rat embryo fibroblasts. eIF-4E alone can transform rat embryo fibroblasts when selection is applied. The pattern of transformation by eIF-4E is similar to that of p21 Ras, raising the possibility that eIF-4E shares a common signal transduction pathway with p21 Ras.

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confidence: 99%

The mRNA 5' Cap-Binding Protein, eIF-4E, Cooperates with v-myc or E1A in the Transformation of Primary Rodent Fibroblasts

Lazaris-Karatzas

Sonenberg

1992

Molecular and Cellular Biology

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Mechanism of action of developmentally regulated sea urchin inhibitor of eIF‐4

Jagus¹,

Huang

Hiremath

et al. 1993

Dev. Genet.

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The developmentally regulated inhibitor of eIF-4 function found in unfertilized sea urchin eggs has been partially purified and its mechanism of action studied in vitro using purified recombinant eIF-4 alpha and cell-free translation systems. The results demonstrate that although the phosphorylation of eIF-4 alpha is necessary to promote protein synthesis, it is not sufficient to maintain all aspects of eIF-4 function. The egg inhibitor does not change eIF-4 alpha phosphorylation state. During the blockage of initiation caused by the egg inhibitor, eIF-4 alpha remains phosphorylated but accumulates in a 48S initiation intermediate. This suggests that the egg inhibitor functions by preventing the release of eIF-4 alpha from the small ribosomal subunit. The characteristics of the inhibitor in a reticulocyte translation system demonstrate that eIF-4 activity is inhibited within 3-6 min. However, the inhibitor's characteristics in a mRNA-dependent translation system contrast with this. Preincubation with the inhibitor for 5-25 min prior to the addition of mRNA does not prevent endogenous eIF-4 from participating in translation but diminishes its ability to be reutilized, consistent with the accumulation of eIF-4 alpha on the small ribosomal subunit. The ribosomal localization of the inhibitor suggests that it could prevent eIF-4 alpha release by direct binding. The gradual inactivation of the inhibitor following fertilization indicates that it represents a component of a novel regulatory cascade that modulates eIF-4 activity.

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Role of protein phosphorylation in TNF‐induced apoptosis: Phosphatase inhibitors synergize with TNF to activate DNA fragmentation in normal as well as TNF‐resistant U937 variants

Wright

Zheng

Zhong

et al. 1993

J of Cellular Biochemistry

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This study examined the role of protein phosphorylation in TNF induction of apoptosis in several tumor cell lines by testing the effects of agents that either stimulate or inhibit protein phosphorylation. The serine-threonine phosphatase inhibitors, okadaic acid (OKA) and calyculin A (CLA), synergistically augmented TNF-induced apoptosis in several TNF-sensitive tumor cell lines including the U937 histiocytic lymphoma, the BT-20 mammary carcinoma, and the LNCap prostatic tumor cell line. Furthermore, the phosphatase inhibitors completely reversed the TNF resistance of a variant (U9-TR) derived from U937. CLA also inhibited phosphatase activity in cell-free extracts from both U937 and U9-TR at the same concentrations (0.4-2.0 nM) that it synergized with TNF. In contrast, TNF treatment of U937 cells did not result in inhibition of phosphatase activity mediated by protein phosphatase 1 (PP1) and PP2A in cell extracts. Since the phosphatase inhibitors are known to increase the overall levels of protein phosphorylation in cells, this suggested that TNF may act by stimulating protein kinase (PK) activity. This hypothesis was supported by the results of testing a panel of relatively specific protein kinase inhibitors. TNF activation of DNA fragmentation was blocked by a potent inhibitor of myosin light chain kinase (MLCK) but was unaffected by inhibitors of cAMP or cGMP-dependent PKs. We postulate that a defect in the activation of MLCK or possibly some other as yet unknown PK may be responsible for the TNF resistance of U9-TR. Furthermore, this resistance may be circumvented by promoting protein phosphorylation with the serine-threonine-dependent phosphatase inhibitors.

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Phosphorylation of the proto-oncogene product eukaryotic initiation factor 4E is a common cellular response to tumor necrosis factor.

Cited by 33 publications

References 28 publications

The mRNA 5' Cap-Binding Protein, eIF-4E, Cooperates with v-myc or E1A in the Transformation of Primary Rodent Fibroblasts

The mRNA 5' Cap-Binding Protein, eIF-4E, Cooperates with v-myc or E1A in the Transformation of Primary Rodent Fibroblasts

Mechanism of action of developmentally regulated sea urchin inhibitor of eIF‐4

Role of protein phosphorylation in TNF‐induced apoptosis: Phosphatase inhibitors synergize with TNF to activate DNA fragmentation in normal as well as TNF‐resistant U937 variants

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