Translational dynamics

Nygård, Odd; Nilsson, Lars

doi:10.1111/j.1432-1033.1990.tb19087.x

Cited by 156 publications

(84 citation statements)

References 287 publications

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“…Consistent with this observation and the data presented here, we have recently demonstrated that a dominant-interfering p70 s6k and a rapamycin-resistant p70 s6k either suppressed 5ЈTOP translation or prevented rapamycin-induced runoff of these transcripts from polysomes, respectively (28a). Given the specificity of p70 s6k for S6 and the location of the ribosomal protein at or near the 40S ribosomal mRNA binding site (51), the prediction would be that the effects of p70 s6k are mediated through S6 phosphorylation, a model presently under examination.…”

Section: Discussionmentioning

confidence: 99%

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The Insulin-Induced Signalling Pathway Leading to S6 and Initiation Factor 4E Binding Protein 1 Phosphorylation Bifurcates at a Rapamycin-Sensitive Point Immediately Upstream of p70^s6k

Manteuffel

Dennis

Pullen

et al. 1997

Molecular and Cellular Biology

226

167

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Employing specific inhibitors and docking-site mutants of growth factor receptors, recent studies have indicated that the insulin-induced increase in 40S ribosomal protein S6 and initiation factor 4E binding protein 1 (4E-BP1) phosphorylation is mediated by the mTOR/FRAP-p70 s6k signal transduction pathway. However, it has not been resolved whether the phosphorylation of both proteins is mediated by p70 s6k or whether they reside on parallel pathways which bifurcate upstream of p70 s6k . Here we have used either rapamycin-resistant, kinase-dead, or wild-type p70 s6k variants to distinguish between these possibilities. The rapamycin-resistant p70 s6k , which has high constitutive activity, was able to signal to S6 in the absence of insulin and to prevent the rapamycin-induced block of S6 phosphorylation. This same construct did not increase the basal state of 4E-BP1 phosphorylation or protect it from the rapamycin-induced block in phosphorylation. Unexpectedly, the rapamycin-resistant p70 s6k inhibited insulin-induced 4E-BP1 phosphorylation in a dose-dependent manner. This effect was mimicked by the kinase-dead and wild-type p70 s6k constructs, which also blocked insulininduced dissociation of 4E-BP1 from initiation factor 4E. Both the kinase-dead and wild-type constructs also blocked reporter p70 s6k activation, although only the kinase-dead p70 s6k had a dominant-interfering effect on S6 phosphorylation. Analysis of phosphopeptides from reporter 4E-BP1 and p70 s6k revealed that the kinasedead p70 s6k affected the same subset of sites as rapamycin in both proteins. The results demonstrate, for the first time, that activated p70 s6k mediates increased S6 phosphorylation in vivo. Furthermore, they show that increased 4E-BP1 phosphorylation is controlled by a parallel signalling pathway that bifurcates immediately upstream of p70 s6k , with the two pathways sharing a common rapamycin-sensitive activator.In insulin-responsive cells, hormonal stimulation provokes the coordinate activation of a complex network of signalling pathways which are involved in the regulation of specific metabolic processes (71). Critical among these affected metabolic processes is the activation and maintenance of high rates of protein synthesis, leading to both global and selective changes in the pattern of translation (14,23,56). Recent studies have suggested that in insulin-sensitive tissues, such as liver, heart, skeletal muscle, and adipose tissue, the increase in protein synthesis is triggered by ligand-induced activation of the receptor and propagated intracellularly through the phosphorylation of the insulin receptor substrate IRS-1 (66). IRS-1 is thought to mediate the insulin signal by inducing the activation of distinct kinases which then target specific components of the translational apparatus (45). In several cases, there is considerable knowledge concerning the functional roles of specific translational components in protein synthesis and of the effect of phosphorylation on their individual activities (48, 65). Much less is k...

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Section: Discussionmentioning

confidence: 99%

“…S6 is an integral 40S ribosomal protein which resides near or at the mRNA binding site, on that surface of the subunit which interacts directly with the larger 60S ribosomal subunit (51). Mitogen stimulation of cells to proliferate leads to multiple, ordered phosphorylation of S6 at five serines which are located at the carboxy terminus of the protein (3,33).…”

mentioning

confidence: 99%

The Insulin-Induced Signalling Pathway Leading to S6 and Initiation Factor 4E Binding Protein 1 Phosphorylation Bifurcates at a Rapamycin-Sensitive Point Immediately Upstream of p70^s6k

Manteuffel

Dennis

Pullen

et al. 1997

Molecular and Cellular Biology

226

167

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“…The RPS6 protein is a part of the small head region of the 40 S subunit, which is a central location for interactions with mRNA, tRNA, and factors that drive initiation of translation (52). The C terminus of RPS6 is sequentially phosphorylated on five serine residues in response to a variety of stimuli and developmental cues (53,54).…”

Section: Conservation Of Covalent Modifications Between Eukaryoticmentioning

confidence: 99%

Analysis of the Arabidopsis Cytosolic Ribosome Proteome Provides Detailed Insights into Its Components and Their Post-translational Modification

Carroll¹,

Heazlewood²,

Ito³

et al. 2008

Molecular & Cellular Proteomics

184

250

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Finding gene-specific peptides by mass spectrometry analysis to pinpoint gene loci responsible for particular protein products is a major challenge in proteomics especially in highly conserved gene families in higher eukaryotes. We used a combination of in silico approaches coupled to mass spectrometry analysis to advance the proteomics insight into Arabidopsis cytosolic ribosomal composition and its post-translational modifications. In silico digestion of all 409 ribosomal protein sequences in Arabidopsis defined the proportion of theoretical genespecific peptides for each gene family and highlighted the need for low m/z cutoffs of MS ion selection for MS/MS to characterize low molecular weight, highly basic ribosomal proteins. We undertook an extensive MS/MS survey of the cytosolic ribosome using trypsin and, when required, chymotrypsin and pepsin. We then used custom software to extract and filter peptide match information from Mascot result files and implement high confidence criteria for calling gene-specific identifications based on the highest quality unambiguous spectra matching exclusively to certain in silico predicted gene-or gene family-specific peptides. This provided an in-depth analysis of the protein composition based on 1446 high quality MS/MS spectra matching to 795 peptide sequences from ribosomal proteins. These identified peptides from five gene families of ribosomal proteins not identified previously, providing experimental data on 79 of the 80 different types of ribosomal subunits. We provide strong evidence for gene-specific identification of 87 different ribosomal proteins from these 79 families. We also provide new information on 30 specific sites of co-and post-translational modification of ribosomal proteins in Arabidopsis by initiator methionine removal, N-terminal acetylation, N-terminal methylation, lysine N-methylation, and phosphorylation. These sitespecific modification data provide a wealth of resources for further assessment of the role of ribosome modification in influencing translation in Arabidopsis. Molecular & Cellular Proteomics 7:347-369, 2008.Ribosomes are large ribonucleoprotein complexes that catalyze the peptidyltransferase reaction in polypeptide synthesis and are thus responsible for the translation of transcripts encoded in cellular genomes. These complexes play the most fundamental role of any protein complex in the generation of the cellular proteome as a whole. Ribosomes consist of two subunits, large and small, but the internal composition of these subunits and their macromolecular size varies between bacteria, animals, fungi, and plants. Both these subunits are composed on rRNA and protein (r-protein) 1 components. Among eukaryotes the 80 S cytosolic ribosomes of the yeast (Saccharomyces cerevisiae), rat (Rattus norvegicus), and human (Homo sapiens) have been the most extensively investigated. These studies have revealed four distinct rRNAs, the 18 S rRNA of the 40 S subunit and 5, 5.8, and 23 S rRNAs of the 60 S subunit. Up to 79 distinct proteins are part ...

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“…Translational elongation in eukaryotic organisms is dependent upon the two soluble elongation factors EF-1 and EF-2, which are functionally analogous to the prokaryotic factors EF-Tu and EF-G, respectively (for reviews see Hinnebusch & Liebman, 1991 ; Merrick, 1992 ;Nygard & Nilsson, 1990 ;Tuite, 1989). However, a third elongation factor (EF-3) is required for translation in fungi (for review see Belfield & Tuite, 1993).…”

Section: Introductionmentioning

confidence: 99%

Regulation of the gene encoding translation elongation factor 3 during growth and morphogenesis in Candida albicans

et al. 1994

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The level of the T€F3 mRNA, which encodes the fungal-specific translation elongation factor 3 (EF-3), was measured during the yeast-to-hyphal transition in Candida albicans. In contrast to a previous report, T€F3 mRNA levels were shown to change during dilution into fresh medium, increasing only transiently when dimorphism was induced by either (i) an increase in growth temperature (from 25 "C to 37 "C) combined with the addition of 10% (vh) bovine calf serum to the medium, or (ii) an increase in growth temperature (from 25 "C to 37 "C) combined with an increase in the pH of the medium (from pH 4 5 to 6.5). T€F3 mRNA levels also increased in control cultures under conditions where germ tubes were not formed, but they remained elevated in contrast t o cultures undergoing morphological changes. E F 3 mRNA levels were not significantly affected by heat-shock, but were tightly regulated during batch growth of the yeast form, reaching maximal levels in exponential phase. Therefore, the changes in T€F3 expression that accompany the dimorphic transition in C. albicans appear to reflect the underlying physiological changes that occur during morphogenesis and are not a response to morphogenesis per se. For this reason T€F3 mRNA measurement cannot be used as a loading control in Northern analyses of dimorphic gene regulation. Comparison of TEF3 mRNA levels with the abundance of the EF-3 polypeptide indicated that the synthesis of this essential translation factor might be subject to post-transcriptional regulation.

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Translational dynamics

Cited by 156 publications

References 287 publications

The Insulin-Induced Signalling Pathway Leading to S6 and Initiation Factor 4E Binding Protein 1 Phosphorylation Bifurcates at a Rapamycin-Sensitive Point Immediately Upstream of p70^s6k

The Insulin-Induced Signalling Pathway Leading to S6 and Initiation Factor 4E Binding Protein 1 Phosphorylation Bifurcates at a Rapamycin-Sensitive Point Immediately Upstream of p70^s6k

Analysis of the Arabidopsis Cytosolic Ribosome Proteome Provides Detailed Insights into Its Components and Their Post-translational Modification

Regulation of the gene encoding translation elongation factor 3 during growth and morphogenesis in Candida albicans

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Translational dynamics

Cited by 156 publications

References 287 publications

The Insulin-Induced Signalling Pathway Leading to S6 and Initiation Factor 4E Binding Protein 1 Phosphorylation Bifurcates at a Rapamycin-Sensitive Point Immediately Upstream of p70s6k

The Insulin-Induced Signalling Pathway Leading to S6 and Initiation Factor 4E Binding Protein 1 Phosphorylation Bifurcates at a Rapamycin-Sensitive Point Immediately Upstream of p70s6k

Analysis of the Arabidopsis Cytosolic Ribosome Proteome Provides Detailed Insights into Its Components and Their Post-translational Modification

Regulation of the gene encoding translation elongation factor 3 during growth and morphogenesis in Candida albicans

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The Insulin-Induced Signalling Pathway Leading to S6 and Initiation Factor 4E Binding Protein 1 Phosphorylation Bifurcates at a Rapamycin-Sensitive Point Immediately Upstream of p70^s6k

The Insulin-Induced Signalling Pathway Leading to S6 and Initiation Factor 4E Binding Protein 1 Phosphorylation Bifurcates at a Rapamycin-Sensitive Point Immediately Upstream of p70^s6k