Differential kinetics of changes in the state of phosphorylation of ribosomal protein S6 and in the rate of protein synthesis in MPC 11 cells during tonicity shifts.

Kruppa, Joachim; Clemens, Mike

doi:10.1002/j.1460-2075.1984.tb01767.x

Cited by 50 publications

(25 citation statements)

References 31 publications

(15 reference statements)

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“…The phosphorylation of S6 lagged behind that of eIF4E and 4E-BP1 and the increase in the rate of protein synthesis during the recovery period. These data are in agreement with previous findings with MPC11 cells in showing that changes in S6 phosphorylation are too slow to account for rapid changes in protein synthesis following tonicity shifts (39).…”

Section: De Novo Initiation Of Protein Synthesis Does Not Require Incsupporting

confidence: 93%

Phosphorylation of Eukaryotic Initiation Factor (eIF) 4E Is Not Required for de Novo Protein Synthesis following Recovery from Hypertonic Stress in Human Kidney Cells

Morley

Naegele

2002

Journal of Biological Chemistry

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Previous work has suggested that increased phosphorylation of eukaryotic initiation factor (eIF) 4E at Ser-209 in the C-terminal loop of the protein often correlates with increased translation rates. However, the functional consequences of phosphorylation have remained contentious with our understanding of the role of eIF4E phosphorylation in translational control far from complete. To investigate the role for eIF4E phosphorylation in de novo translation, we studied the recovery of human kidney cells from hypertonic stress. Results show that hypertonic shock caused a rapid inhibition of protein synthesis and the disaggregation of polysomes. These changes were associated with the dephosphorylation of eIF4G, eIF4E, 4E-binding protein 1 (4E-BP1), and ribosomal protein S6. In addition, decreased levels of the eIF4F complex and increased association of 4E-BP1 with eIF4E were observed over a similar time course. The return of cells to isotonic medium rapidly promoted the phosphorylation of these initiation factors, increased levels of eIF4F complexes, promoted polysome assembly, and increased rates of translation. However, by using a cell-permeable, specific inhibitor of eIF4E kinase, Mnk1 (CGP57380), we show that de novo initiation of translation and eIF4F complex assembly during this recovery phase did not require eIF4E phosphorylation.

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Section: De Novo Initiation Of Protein Synthesis Does Not Require Incsupporting

confidence: 93%

Phosphorylation of Eukaryotic Initiation Factor (eIF) 4E Is Not Required for de Novo Protein Synthesis following Recovery from Hypertonic Stress in Human Kidney Cells

Morley

Naegele

2002

Journal of Biological Chemistry

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“…One way or another, if the hairpin in B13hp is stabilized, the 40S ribosomal subunit should stall before it reaches the ATG codon, a prediction which I am in the process of testing. A second consequence of shifting to hypertonic medium is a drastic reduction in the overall translational capacity (38,54) which must force mRNAs to compete for the small, residual capacity. Two incidental observations are readily explained if one accepts that mRNAs must compete in salt-stressed cells.…”

Section: Methodsmentioning

confidence: 99%

Leader length and secondary structure modulate mRNA function under conditions of stress.

Kozak

1988

Mol. Cell. Biol.

155

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Simian virus 40-based plasmids that direct the synthesis of preproinsulin in cultured monkey cells were used to study the effects of mRNA structure on translational efficiency. Lengthening the leader sequence enhanced translation in this system. The enhancement was most obvious when an unstructured sequence (two, four, or eight copies of the oligonucleotide AGCTAAGTAAGTAAGTA) was inserted upstream from a region of deliberate secondary structure; the degree of enhancement was proportional to the number of copies of the inserted oligonucleotide. Lengthening the leader sequence on the 3' side of a stem-and-loop structure, in contrast, did not offset the potentially inhibitory effect of the hairpin structure. Both the facilitating effect of length and the inhibitory effect of secondary structure were demonstrated most easily under conditions of mRNA competition, which was brought about by an abrupt shift in the tonicity of the culture medium. These experiments suggest a simple structural basis for the long-recognized differential response of viral and cellular mRNAs to hypertonic stress. The fact that the translatability of structure-prone mRNAs varies with changes in the environment may also have general implications for gene expression in eucaryotic cells.A recent survey of vertebrate mRNA sequences (37) revealed that 75% of the characterized mRNAs have 5'-untranslated sequences that range in length from 20 to 100 nucleotides. About one-fourth of the mRNAs surveyed had leader sequences in the range of 100 to 300 nucleotides, and there were rare examples of mRNAs with 5'-noncoding sequences as long as 1,000 nucleotides (52). It is not clear how leader length affects translational efficiency, since both extremes are found among efficiently translated cellular and viral mRNAs. For example, the tripartite leader sequence on adenovirus late mRNAs (63) and the leader sequences on some heat shock mRNAs (27) are more than 200 nucleotides long, while the mRNAs that encode adenovirus polypeptide IX and the N protein of vesicular stomatitis virus have leader sequences of only 24 and 13 nucleotides, respectively (13, 63). Because length is not the only variable when one natural mRNA is compared with another, however, the question of how leader length affects translational efficiency cannot be decided by inspecting natural mRNAs; a more systematic approach is needed. The question has been addressed experimentally in two preliminary studies, one which reported no effect of expanding the leader sequence (25) and the other which reported that inserting an extra 152 nucleotides lowered the translational yield (4). The experiments reported here indicate that expanding the leader sequence on a chimeric preproinsulin mRNA enhances its translation under conditions of mRNA competition which occur, for example, when cells in culture are shifted to hypertonic medium.The "wild-type" mRNA used for these studies consisted of the rat preproinsulin TI-coding sequence linked to the 5'-untranslated sequence of the message that encodes simian vi...

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“…It has been known for decades that hypertonic stress induced by sorbitol treatment of cells reversibly decreases the phosphorylation of S6K, as well as the overall translational output of the cell (Saborio et al, 1974;Kruppa and Clemens, 1984), but mechanisms to explain how this occurs have only recently been proposed. One suggested mechanism is that osmotic stress induced by sorbitol treatment causes a rapid and reversible disintegration of the mitochondrial proton gradient.…”

Section: Osmotic Stressmentioning

confidence: 99%

Upstream of the mammalian target of rapamycin: do all roads pass through mTOR?

2006

Oncogene

348

309

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The mammalian target of rapamycin (mTOR) is a serine/ threonine kinase that controls many aspects of cellular physiology, including transcription, translation, cell size, cytoskeletal organization and autophagy. Recent advances in the mTOR signaling field have found that mTOR exists in two heteromeric complexes, mTORC1 and mTORC2. The activity of mTORC1 is regulated by the integration of many signals, including growth factors, insulin, nutrients, energy availability and cellular stressors such as hypoxia, osmotic stress, reactive oxygen species and viral infection. In this review we highlight recent advances in the mTOR signaling field that relate to how the two mTOR complexes are regulated, and we discuss stress conditions linked to the mTOR signaling network that have not been extensively covered in other reviews. Given the diversity of signals that have been shown to impinge on mTOR, we also speculate on other signaltransduction pathways that may be linked to mTOR in the future.

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Differential kinetics of changes in the state of phosphorylation of ribosomal protein S6 and in the rate of protein synthesis in MPC 11 cells during tonicity shifts.

Cited by 50 publications

References 31 publications

Phosphorylation of Eukaryotic Initiation Factor (eIF) 4E Is Not Required for de Novo Protein Synthesis following Recovery from Hypertonic Stress in Human Kidney Cells

Phosphorylation of Eukaryotic Initiation Factor (eIF) 4E Is Not Required for de Novo Protein Synthesis following Recovery from Hypertonic Stress in Human Kidney Cells

Leader length and secondary structure modulate mRNA function under conditions of stress.

Upstream of the mammalian target of rapamycin: do all roads pass through mTOR?

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