Protein synthesis and protein phosphorylation during heat stress, recovery, and adaptation.

Duncan, Roger; Hershey, John W.B.

doi:10.1083/jcb.109.4.1467

Cited by 185 publications

(108 citation statements)

References 53 publications

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“…40s-ribosome complexes [l]; disruption of eIF-3 . eIF-4F complexes in response to poliovirus infection [62, 631 or heat shock [23] correlates with selective translational controls. Since phosphorylation of eIF-4a has no effect on its binding to m7GTP affinity resins [I, 7, 91 and only the phosphorylatable form is associated with the 48s initiation complex, it is not unreasonable to expect that phosphorylation could affect its association with other initiation factors such as eIF4y, eIF-3, eIF-4B, or with ribosomal protein S6 to mediate selective translation of repressed mRNA [l, 6, 13, 601.…”

Section: Discussionmentioning

confidence: 99%

“…Increased levels of eIF4a phosphorylation are also seen in src-transformed [17] and ras-transformed fibroblasts [21]. Conversely, phosphorylation decreases under conditions in which protein synthesis is inhibited, such as during mitosis 1221, in response to heat shock [23,241 and folIowing adenovirus [25l or influenza virus infection [25a]. A mutant form of eIF4a in which Ser53 was replaced with an alanine residue (Ala53) could not be incorporated into initiation complexes, suggesting that eIF-4a phosphorylation is essential for mediating the binding of mRNA to the 43s initiation complex [26].…”

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confidence: 99%

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Increased phosphorylation of eukaryotic initiation factor 4α during early activation of T lymphocytes correlates with increased initiation factor 4F complex formation

Morley

Rau

Kay

et al. 1993

European Journal of Biochemistry

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Mature porcine peripheral blood mononuclear cells (PPBMCs) exist in a resting state both in vivo and when maintained in culture, with low translation rates consistent with their non-proliferative state. When cultured in the presence of the appropriate mitogen, there is a 2-4-fold increase in the rate of protein synthesis per ribosome within 4 h of stimulation [Kay, J. E., Ahern, T. and In these studies, we have demonstrated that activation of quiescent PPBMCs with the phorbol ester phorbol 12-myristate 13-acetate or concanavalin A leads to a rapid 2-4-fold increase in the rate of protein synthesis within 1 h or 4 h, respectively, which is insensitive to the transcriptional inhibitor, 5,6-dichlorobenzimidazole riboside. Relative to control cells, both phorbol ester and concanavalin A induce a 2-4-fold increase in labelling of the eukaryotic initiation factor eIF4a with phosphate in vivo, which primarily reflects a small net increase in phosphorylation rather than phosphate turnover on eIF-4a. Similarly, with the human leukaemic T cell line JURKAT, stimulation of the T cell receptor with the monoclonal antibody, OKT-3, or treatment with phorbol ester induces a 2-3-fold increase in eIF4a phosphorylation within 30 min. Analysis of phosphorylation by twodimensional gel electrophoresis and measurement of kinase activity towards synthetic peptides, indicate that this increased labelling also reflects increased eIF4a kinase activity rather than phosphate turnover on eIF-4a.Of central importance is the finding that, concomitant with increased rates of protein synthesis following stimulation of PPBMCs with either phorbol ester or concanavalin A, there is a significant increase in the level of eIF4a recovered in high-molecular-mass complexes. These data suggest that, in quiescent PPBMCs, eIF-4F may be limiting and that the association of eIF4a and eIF-4y into high-molecular-mass complexes is regulated by phosphorylation and may play a pivotal role in translational control.Control of polypeptide synthesis plays an important role in cell proliferation (reviewed in [l]) and translation rates generally reflect the growth state of the cultured eukaryotic cell. Physiological regulation of protein synthesis is almost always exerted at the level of polypeptide initiation [2, 31. Numerous studies have indicated key roles in the regulation of protein synthesis for structural features of mRNA molecules; these include the presence of the 5'-terminal cap structure, the primary and secondary structure of the 5'-un-

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Increased phosphorylation of eukaryotic initiation factor 4α during early activation of T lymphocytes correlates with increased initiation factor 4F complex formation

Morley

Rau

Kay

et al. 1993

European Journal of Biochemistry

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“…Heat shock treatment also induces eIF2␣ phosphorylation that contributes to translational inhibition (34). However, studies have indicated that eIF2␣-independent mechanisms can also contribute to inhibition of translation (11). For example, in heat-shocked cells the canonical translation initiation factor eIF4G is bound by Hsp27 and recruited to SGs, thus inactivating the cap binding complex, eIF4F, and inhibiting translation initiation (9).…”

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confidence: 99%

Stable Formation of Compositionally Unique Stress Granules in Virus-Infected Cells

Piotrowska

Hansen

Park

et al. 2010

J Virol

106

141

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Stress granules are sites of mRNA storage formed in response to a variety of stresses, including viral infections. Here, the mechanisms and consequences of stress granule formation during poliovirus infection were examined. The results indicate that stress granules containing T-cell-restricted intracellular antigen 1 (TIA-1) and mRNA are stably constituted in infected cells despite lacking intact RasGAP SH3-domain binding protein 1 (G3BP) and eukaryotic initiation factor 4G. Fluorescent in situ hybridization revealed that stress granules in infected cells do not contain significant amounts of viral positive-strand RNA. Infection does not prevent stress granule formation in response to heat shock, indicating that poliovirus does not block de novo stress granule formation. A mutant TIA-1 protein that prevents stress granule formation during oxidative stress also prevents formation in infected cells. However, stress granule formation during infection is more dependent upon ongoing transcription than is formation during oxidative stress or heat shock. Furthermore, Sam68 is recruited to stress granules in infected cells but not to stress granules formed in response to oxidative stress or heat shock. These results demonstrate that stress granule formation in poliovirus-infected cells utilizes a transcription-dependent pathway that results in the appearance of stable, compositionally unique stress granules.

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“…Under heat shock conditions and soon after heat shock, the mammalian cap-binding initiation factor eIF4E is impaired (13)(14)(15)(16)(17) and the abundance of eIF4F complexes is reduced (14). In addition, 4E-BPs, repressors of eIF4E, become activated under these conditions due to their hypophosphorylation (18,19).…”

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confidence: 99%

Distinctive Properties of the 5′-Untranslated Region of Human Hsp70 mRNA

Rubtsova

Sizova

Dmitriev

et al. 2003

Journal of Biological Chemistry

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A relaxed cap-dependence of translation of the mRNA-encoding mammalian heat shock protein Hsp70 may suggest that its 5 -untranslated region (UTR) possesses an internal ribosome entry site (IRES). In this study, this possibility has been tested in transfected cells using plasmids that express dicistronic mRNAs. Using a reporter gene construct, Renilla luciferase/Photinus pyralis luciferase, we show that the 216-nt long 5 -UTR of Hsp70 mRNA acts as an IRES that directs ribosomes to the downstream start codon by a cap-independent mechanism. The relative activity of this IRES (100-fold over the empty vector) is similar to that of the classical picornaviral IRESs. Additional controls indicate that this high expression of the downstream reporter is not due to readthrough from the upstream cistron, nor is it due to translation of cryptic monocistronic transcripts. The effect of small deletions within the 5 -UTR of Hsp70 mRNA on the IRES activity varies in dependence on their position within the 5 -UTR sequence. With the exception of deletion of nt 33-50, it is small for the 5 -terminal half of the 5 -UTR and rather strong for the 3 -terminal section. However, neither of these small deletions abolishes the IRES activity completely. Excision of larger sections (>50 nt) by truncation of the 5 -UTR from the 5 -end or by internal deleting results in a dramatic impairment of the IRES function. Taken together, these data suggest that the IRES activity of the 5 -UTR of Hsp70 mRNA requires integrity of almost the entire sequence of the 5 -UTR. The data are discussed in terms of a model that allows a three-dimensional rather than linear mode of selection of the initiation region surrounding the start codon of Hsp70 mRNA.

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Protein synthesis and protein phosphorylation during heat stress, recovery, and adaptation.

Cited by 185 publications

References 53 publications

Increased phosphorylation of eukaryotic initiation factor 4α during early activation of T lymphocytes correlates with increased initiation factor 4F complex formation

Increased phosphorylation of eukaryotic initiation factor 4α during early activation of T lymphocytes correlates with increased initiation factor 4F complex formation

Stable Formation of Compositionally Unique Stress Granules in Virus-Infected Cells

Distinctive Properties of the 5′-Untranslated Region of Human Hsp70 mRNA

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