Regulation of translation initiation by FRAP/mTOR.

  title={Regulation of translation initiation by FRAP/mTOR.},
  author={Anne-Claude Gingras and Brian Raught and Nahum Sonenberg},
  journal={Genes \& development},
  volume={15 7},
Regulation of protein synthesis in eukaryotes plays a critical role in development, differentiation, cell cycle progression, cell growth, and apoptosis (Mathews et al. 2000). Translational control allows for a more rapid response than transcriptional modulation because no mRNA synthesis, processing, or transport is required, and can be used to coordinate gene expression in systems that lack transcriptional regulation, such as reticulocytes or platelets (Weyrich et al. 1998; Mathews et al. 2000… 

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The regulation of Pol III transcription by mTOR.

Maf1, a known negative regulator of pol III transcription in yeast, was investigated and it was found to repress transcription of all class III genes in mammalian cells, and this repression can be relieved by the addition of a purified fraction of TFIIIB.

Regulation of Transcription and Translation by Hypoxia

As hypoxia is induced by tumor growth and affects tumor progression and metastasis, unraveling the basis of hypoxic control of transcription and translation will provide a better understanding of cancer physiology and development of anti-tumor therapies.

eIF4E, the mRNA cap-binding protein: from basic discovery to translational research.

  • N. Sonenberg
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    Biochemistry and cell biology = Biochimie et biologie cellulaire
  • 2008
The discovery of eIF4E is described, its mechanism of action in translation initiation, and its role in the control of cancer and innate immunity are described.

Initiation factor modifications in the preapoptotic phase

How the functions of polypeptide chain initiation factors and of other proteins with which they interact may be altered as a result of activation of apoptosis are indicated and the potential significance of such changes for translational control and cell growth regulation is discussed.

Translational regulation in cell stress and apoptosis. Roles of the eIF4E binding proteins

  • M. Clemens
  • Biology
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  • 2001
Changes in the state of phosphorylation of the 4E‐BPs and in the extent of their association with eIF4E occur at an early stage in the response of cells to apoptotic inducers, affecting the control of protein synthesis, cell proliferation and cell survival.

Initiation of protein biosynthesis in eukaryotes

Regulation of translation focuses mostly on controlling the activity of either eIF2 or eIF4F and this regulation has different consequences, whereas reduction in eif4F activity drives competition between mRNAs.



22 Translational Control of TOP mRNAs

It seems that resources and energy are wasted by resting cells for maintaining a large excess of inefficiently translated mRNAs, but this actually enables them to respond rapidly to mitogenic stimulations by having immediately available a large protein synthesis capacity.

6 Regulation of Ribosomal Recruitment in Eukaryotes

The current understanding of how the activity of the eIF4 initiation factors is regulated by intracellular signaling pathways is described, and the current under-standing of this chapter is summarized.

13 Translational Control of Ribosomal Protein mRNAs in Eukaryotes

This chapter focuses on the translational control of messenger RNAs encoding both ribosomal proteins and several related proteins during development, with fluctuations in growth rate and upon hormonal stimulation, as studied in various eukaryotic organisms and cell lines.

16 Regulation of Translation Initiation in Mammalian Cells by Amino Acids

Recent evidence is summarized that supports a predominant role for amino acids in the regulation of protein synthesis in mammalian cells through a mechanism involving the protein kinase mTOR.

TOR controls translation initiation and early G1 progression in yeast.

It is proposed that the TORs, two related phosphatidylinositol kinase homologues, are part of a novel signaling pathway that activates eIF-4E-dependent protein synthesis and, thereby, G1 progression in response to nutrient availability and may constitute a checkpoint that prevents early G 1 progression and growth in the absence of nutrients.

Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae.

Yeast control of ribosome biosynthesis by the TOR pathway is surprisingly complex and it is found that TOR signaling is a prerequisite for the induction of r-protein gene transcription that occurs in response to improved nutrient conditions.

Translational Control of the Antiapoptotic Function of Ras*

It is established that eIF4E-dependent protein synthesis is essential for survival of fibroblasts bearing oncogenic Ras and support the concept that activation of cap-dependent translation by extracellular ligands or intrinsic survival signaling molecules suppresses apoptosis, whereas synthesis of proteins mediating apoptosis can occur independently of the cap.

Nutrients differentially regulate multiple translation factors and their control by insulin.

Data show that activation by insulin of p70 S6 kinase, which modulates the translation of specific mRNAs, depends on the availability of amino acids whereas regulation of factors involved in overall activation of translation (eIF2B, eEF2) requires both amino acids and glucose.

14 Ribosomal Protein S6 Phosphorylation and Signal Transduction

It has become evident during the last 5–10 years that the major intracellular mediator of these events is protein phosphorylation/dephosphorylation (Krebs 1994); the realization of the importance of this regulatory mechanism to cell growth has focused a great deal of attention on the identification of substrates and the signaling pathways that control cell cycle progression.

Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast.

Inactivation of the uORF accelerates the completion of Start and entry into the cell cycle suggesting that translational regulation of CLN3 provides a mechanism coupling cell growth and division.