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Translational regulation of terminal oligopyrimidine mRNAs induced by serum and amino acids involves distinct signaling events

Translational regulation of terminal oligopyrimidine mRNAs induced by serum and amino acids involves distinct signaling events
Translational regulation of terminal oligopyrimidine mRNAs induced by serum and amino acids involves distinct signaling events
Various mitogenic or growth inhibitory stimuli induce a rapid change in the association of terminal oligopyrimidine (TOP) mRNAs with polysomes. It is generally believed that such translational control hinges on the mammalian target of rapamycin (mTOR)-S6 kinase pathway. Amino acid availability affects the translation of TOP mRNAs, although the signaling pathway involved in this regulation is less well characterized. To investigate both serum- and amino acid-dependent control of TOP mRNA translation and the signaling pathways involved, HeLa cells were subjected to serum and/or amino acid deprivation and stimulation. Our results indicate the following. 1) Serum and amino acid deprivation had additive effects on TOP mRNA translation. 2) The serum content of the medium specifically affected TOP mRNA translation, whereas amino acid availability affected both TOP and non-TOP mRNAs. 3) Serum signaling to TOP mRNAs involved only a rapamycin-sensitive pathway, whereas amino acid signaling depended on both rapamycin-sensitive and rapamycin-insensitive but wortmannin-sensitive events. 4) Eukaryotic initiation factor-2 phosphorylation increased during amino acid deprivation, but not following serum deprivation. Interestingly, rapamycin treatment suggests a novel connection between the mTOR pathway and eukaryotic initiation factor-2 phosphorylation in mammalian cells, which may not, however, be involved in TOP mRNA translational regulation.
0021-9258
13522-13531
Caldarola, S.
42fb4011-afd4-4fcc-8763-f5893cb19871
Amaldi, F.
0a5ec13b-72e0-4af2-933a-90eaa73e44c7
Proud, C.G.
c2cc50f9-4565-4d59-9dfc-aa70b9268a6e
Loreni, F.
f0125769-b7b9-45f2-8a63-56c2ed96f19e
Caldarola, S.
42fb4011-afd4-4fcc-8763-f5893cb19871
Amaldi, F.
0a5ec13b-72e0-4af2-933a-90eaa73e44c7
Proud, C.G.
c2cc50f9-4565-4d59-9dfc-aa70b9268a6e
Loreni, F.
f0125769-b7b9-45f2-8a63-56c2ed96f19e

Caldarola, S., Amaldi, F., Proud, C.G. and Loreni, F. (2004) Translational regulation of terminal oligopyrimidine mRNAs induced by serum and amino acids involves distinct signaling events. The Journal of Biological Chemistry, 279 (14), 13522-13531. (doi:10.1074/jbc.M310574200).

Record type: Article

Abstract

Various mitogenic or growth inhibitory stimuli induce a rapid change in the association of terminal oligopyrimidine (TOP) mRNAs with polysomes. It is generally believed that such translational control hinges on the mammalian target of rapamycin (mTOR)-S6 kinase pathway. Amino acid availability affects the translation of TOP mRNAs, although the signaling pathway involved in this regulation is less well characterized. To investigate both serum- and amino acid-dependent control of TOP mRNA translation and the signaling pathways involved, HeLa cells were subjected to serum and/or amino acid deprivation and stimulation. Our results indicate the following. 1) Serum and amino acid deprivation had additive effects on TOP mRNA translation. 2) The serum content of the medium specifically affected TOP mRNA translation, whereas amino acid availability affected both TOP and non-TOP mRNAs. 3) Serum signaling to TOP mRNAs involved only a rapamycin-sensitive pathway, whereas amino acid signaling depended on both rapamycin-sensitive and rapamycin-insensitive but wortmannin-sensitive events. 4) Eukaryotic initiation factor-2 phosphorylation increased during amino acid deprivation, but not following serum deprivation. Interestingly, rapamycin treatment suggests a novel connection between the mTOR pathway and eukaryotic initiation factor-2 phosphorylation in mammalian cells, which may not, however, be involved in TOP mRNA translational regulation.

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Published date: 1 April 2004

Identifiers

Local EPrints ID: 56515
URI: http://eprints.soton.ac.uk/id/eprint/56515
ISSN: 0021-9258
PURE UUID: 3afdcfd4-38c6-450b-985d-b0fbdb7eef79

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Date deposited: 07 Aug 2008
Last modified: 15 Mar 2024 11:02

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Contributors

Author: S. Caldarola
Author: F. Amaldi
Author: C.G. Proud
Author: F. Loreni

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