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The catabolic capacity of Saccharomyces cerevisiae is preserved to a higher extent during carbon compared to nitrogen starvation.

A comparison of catabolic capacity was made between S. cerevisiae cells subjected to 24 h carbon or nitrogen starvation. The cells were shifted to starvation conditions at the onset of respiratory growth on ethanol in aerobic batch cultures, using glucose as the carbon and energy source. The results showed that the catabolic capacity was preserved to a much larger extent during carbon compared to nitrogen starvation. Nitrogen starvation experiments were made in the presence of ethanol (not glucose) to exclude the effect of glucose transport inactivation (Busturia and Lagunas, 1986). Hence, the difference in catabolic capacity could not be attributed to differences in glucose transport capacity during these conditions. In order to understand the reason for this difference in starvation response, measurement of protein composition, adenine nucleotides, inorganic phosphate, polyphosphate and storage carbohydrates were performed. No clear correlation between any of these variables and catabolic capacity after starvation could be obtained. However, there was a positive correlation between total catabolic activity and intracellular ATP concentration when glucose was added to starved cells. The possible mechanism for this correlation, as well as what determines the ATP level, is discussed.

Adenosine Diphosphate↗

Charging levels of four tRNA species in Escherichia coli Rel(+) and Rel(-) strains during amino acid starvation: a simple model for the effect of ppGpp on translational accuracy.

Escherichia coli strains mutated in the relA gene lack the ability to produce ppGpp during amino acid starvation. One consequence of this deficiency is a tenfold increase in misincorporation at starved codons compared to the wild-type. Previous work had shown that the charging levels of tRNAs were the same in Rel(+) and Rel(-) strains and reduced, at most, two- to fivefold in both strains during starvation. The present reinvestigation of the charging levels of tRNA(2)(Arg), tRNA(1)(Thr), tRNA(1)(Leu) and tRNA(His) during starvation of isogenic Rel(+) and Rel(-) strains showed that starvation reduced charging levels tenfold to 40-fold. This reduction corresponds much better with the decreased rate of protein synthesis during starvation than that reported earlier. The determination of the charging levels of tRNA(2)(Arg) and tRNA(1)(Thr) during starvation were accurate enough to demonstrate that charging levels were at least fivefold lower in the Rel(-) strain compared to the Rel(+) strain. Together with other data from the literature, these new data suggest a simple model in which mis-incorporation increases as the substrate availability decreases and that ppGpp has no direct effect on enhancing translational accuracy at the ribosome.

Acylation↗

Molecular cloning and characterization of six cDNAs expressed during glucose starvation in excised maize (Zea mays L.) root tips.

In order to isolate glucose-starvation-related cDNAs in maize (Zea mays L.) root tips, a cDNA library was constructed with poly(A)+ mRNA from 24 h starved root tips. After differential screening of the library, we isolated six different cDNAs (named pZSS2 and pZSS7) which were expressed during glucose starvation. Time course analysis revealed that maximum expression of five of these genes occurs 30 h after the onset of the starvation treatment. On the contrary, the expression of mRNAs corresponding to pZSS4 was maximal at an early stage of starvation and then dramatically decreased. The expression of this gene did not seem to be specific for glucose starvation. The pattern of induction of the genes corresponding to pZSS2, pZSS3, pZSS5, pZSS6 and pZSS7 revealed that non-metabolizable sugars such as L-glucose and mannitol induce mRNA transcription similarly to glucose starvation. When D-glucose or any other metabolizable sugar was supplied, the level of transcripts was reduced. Nucleotide sequence analyses of the six cDNAs allowed identification of five of them by comparison with sequence data bases. The protein encoded by clone pZSS2 is analogous to a wound-induced protein from barley. Clones pZSS4 to pZSS7 encode, respectively, a transmembrane protein, a cysteine protease, a metallothionein-like protein and a chymotrypsin/subtilisin-like protease inhibitor. Clone pZSS3 shares no significant homology with any known sequence.

Amino Acid Sequence↗

Comparative analysis of idiA and isiA transcription under iron starvation and oxidative stress in Synechococcus elongatus PCC 7942 wild-type and selected mutants.

In the mesophilic cyanobacterium Synechococcus elongatus PCC 7942, iron starvation induces the expression of a number of proteins, including IdiA and IsiA. Whereas IdiA protects photosystem (PS) II under mild iron limitation against oxidative stress in a yet unknown way, prolonged iron starvation leads to the formation of the PS I-IsiA supercomplex. Transcription of idiA is positively regulated by IdiB under iron starvation, and Fur represses transcription of isiAB under iron-sufficient growth conditions. In this report, data are presented suggesting a strong interrelationship between iron homeostasis and oxidative stress in S. elongatus PCC 7942, and showing that transcription of major iron-regulated genes, such as isiA, isiAB, idiA, idiB, mapA, and irpA, is induced by oxidative stress within a few minutes by treatment of cells with hydrogen peroxide or methylviologen. The overall results suggest that isiA/isiAB as well as idiB transcription in response to oxidative stress might be controlled by a transcriptional repressor possibly of the PerR-type. This fact also explains the observed cross-talk between IdiB- and Fur-mediated transcriptional regulation of gene expression and for the role of H(2)O(2) as a superior trigger coordinating expression of iron-regulated genes under iron starvation and oxidative stress. Measuring 77 K chlorophyll a fluorescence, it is shown that hydrogen peroxide treatment causes a transient short-term modification of PS II and PS I most likely leading to increased cyclic electron transport around PS I. In this context, the intriguing observation was made that idiB is transcribed as part of an operon together with a gene encoding a potential [2Fe-2S]-protein. This protein has similarity to [Fe-S]-proteins involved in the electron transport activity of the NDH I complex in eubacteria. Since the NDH I complex is involved in cyclic electron transport activity around PS I in cyanobacteria and both adaptation to iron starvation and adaptation to oxidative stress lead to an enhanced cyclic electron transport activity around PS I, this potential [Fe-S]-protein might participate in the overall adaptational response to iron starvation and/or oxidative stress in Synechococcus.

Bacterial Proteins↗

Schizosaccharomyces pombe taf1+ is required for nitrogen starvation-induced sexual development and for entering the dormant GO state.

Environmental change, such as nutritional starvation, induces physiological and morphological alterations that enable fission yeast cells to survive. We isolated a novel gene, taf1+, required for the response to nitrogen starvation in the fission yeast Schizosaccharomyces pombe. taf1 disruptants could not mate upon nitrogen starvation, but could upon carbon starvation. taf1 disruptants had a defect in inducing stell+ expression under nitrogen starvation conditions. Furthermore, they lost viability quickly in nitrogen-depleted medium. Unlike wild-type cells, starved taf1-cells had nuclear chromatin that were flat and adhered to the cell periphery. These results indicate that tqf1+ is required for nitrogen starvation-induced sexual development and entering the dormant G0 state.

Amino Acid Sequence↗

The involvement of the RAD6 gene in starvation-induced reverse mutation in Saccharomyces cerevisiae.

The accumulation of Ade+ revertants during adenine starvation and Trp+ revertants during tryptophan starvation in haploid polyauxotrophic strains of Saccharomyces cerevisiae occurs in a time-dependent manner. Accumulation of revertants is enhanced in Rad6- strains, suggesting that starvation-induced reversion is influenced by some of the RAD6 gene functions. The higher frequency of adaptive reversions in Rad6- strains is somewhat influenced by, but does not totally depend on, the genetic background. Therefore, the RAD6 gene product is involved in maintaining a low level not only of spontaneous mutation but also of starvation-induced reversion. The starvation-induced Ade+ and Trp+ reversions both appear to be adaptive. The analysis of growth characteristics and the genotype of revertants shows a difference between early and late-appearing revertants. These results support the hypothesis that the adaptivity of starvation-induced reversion is based on the selective fixation of random mutations, and particularly on transcription-enhanced repair and/or mutagenesis processes.

Adaptation, Physiological↗

3T3-L1 adipocyte glucose transporter (HepG2 class): sequence and regulation of protein and mRNA expression by insulin, differentiation, and glucose starvation.

A glucose transporter cDNA (GLUT) clone was isolated from mouse 3T3-L1 adipocytes and sequenced. The nucleotide and deduced amino acid sequences were, respectively, 95 and 99% homologous to those of the rat brain transporter. The mouse cDNA and a polyclonal antibody recognizing the corresponding in vitro translation product were used to compare changes in transporter mRNA and protein levels during differentiation, glucose starvation, and chronic insulin exposure of 3T3-L1 preadipocytes. The respective cellular content of transporter mRNA and protein were increased 6.6- and 7.8-fold during differentiation, and 3.8- and 2.5-fold from chronic insulin exposure of differentiated adipocytes. Glucose starvation increased transporter mRNA and protein levels 2.2- and 3.5-fold in undifferentiated preadipocytes and 1.8- and 3.1-fold in differentiated adipocytes. Starvation of undifferentiated cells completely converted the native transporter to an incompletely glycosylated form, while increasing basal transport rates 4.5-fold. Either full glycosylation is not required to produce a functionally active transporter, or starvation causes a unique predifferentiation induction of the normally absent "responsive" transporter. The changes in transporter protein expression elicited by differentiation were attributed primarily to increased rates of transporter synthesis, while the disproportionate changes in mRNA and protein expression from chronic insulin treatment and starvation suggested these conditions increase synthesis and decrease turnover rates in regulating transporter protein expression. Although chronic insulin exposure and glucose starvation each raised the expression of transporter protein greater than 3-fold and basal transport rates 2.5- to 4.5-fold, no significant increase in the insulin responsiveness of 3T3-L1 preadipocytes or differentiated adipocytes was observed. Thus, the changes in the transporter mRNA and protein expression observed in this study were most consistent with their being associated with the regulated expression of a basal or low level insulin-responsive transporter.

Adipose Tissue↗

Glucose and fat metabolism during short-term starvation in cirrhosis.

To evaluate the metabolic consequences of short-term (i.e., less than 24 hours) starvation, glucose and fat metabolism were studied in eight healthy subjects and in eight patients with stable cirrhosis after 16-hour and again after 22-hour starvation by 3-[3H]glucose and [14C]palmitate turnover and by indirect calorimetry. Although patients and controls showed significant increases in free fatty acid concentration (respectively, 48% +/- 12% and 53% +/- 17%) and turnover (55% +/- 14% and 71% +/- 21%) during short-term starvation, the values after 16- and after 22-hour starvation were higher in cirrhosis. Fat oxidation was enhanced in the patients, but did not increase during fasting in contrast to controls (increase 19% +/- 17%, P less than 0.05). Net glucose oxidation was decreased in postabsorptive cirrhotics (P less than 0.05). Although postabsorptive glucose turnover was not different from controls, starvation induced a greater decrease in glucose turnover in the patients (25% +/- 3% vs. 10% +/- 3%, P less than 0.05). This was not reflected in plasma glucose concentrations. In conclusion, the effects of starvation on glucose and fat metabolism are enhanced in cirrhosis; fasting hypoglycemia is prevented by decreased use of glucose. It remains to be established whether these changes are merely explained by defective liver function, per se.

Adult↗

Effect of starvation and elective surgery on hand dynamometry and circulating concentration of various proteins.

The effect of 4 days total starvation (water only) in five normal subjects on the circulating concentrations of various proteins was studied. Changes in plasma albumin and total protein concentrations were compared with those of six patients undergoing elective abdominal surgery with partial starvation and six patients undergoing orthopaedic surgery with adequate feeding - (0.126-0.146 MJ/kg/day and 1.2-1.4 g protein/kg/day). In a companion study hand grip strength was measured daily in ten normal subjects during starvation and in 18 patients undergoing surgery for hernia repair (n = 6), cholecystectomy (n = 6) and major abdominal surgery (n = 6). Starvation produced marked reductions (approximately 30%) in the circulating concentrations of retinol binding protein and prealbumin but did not significantly affect the plasma concentration of immunoglobulins (IgG, IgA, IgM) acute phase reactants (orosomucoid, haptoglobin, alpha(1) antitrypsin), albumin and total protein. On the other hand both types of elective surgery produced significant reductions in plasma albumin and total protein concentrations irrespective of feeding. Grip strength was not significantly altered by four days of starvation but surgery produced a temporary reduction in grip strength, the extent and duration of which was related to the severity of operation. This study helps to separate the effect of surgery and starvation on hand dynamometry and circulating protein concentrations and indicates their limitations as indicators of nutritional state.

Journal Article↗

The effects of starvation and refeeding on egg laying and the synthetic activity of the albumen gland in Bulinus truncatus, a snail vector of urinary schistosomiasis.

1. The effects of starvation (for 1, 2, 3, 6, 9 and 12 days, respectively) and refeeding (12 days starvation and 1, 2 and 3 days refeeding, respectively) on egg laying and albumen gland activity in the freshwater snail, Bulinus truncatus were studied. 2. The egg laying of starving snails rapidly decreased and ceased by day 6 of starvation. Egg laying was restored 24 hr after refeeding. The recorded decrease in albumen gland wet weight was proportional to the starvation periods. The DNA contents of the glands of the different experimental groups was not statistically different from the controls. 3. Albumen gland synthetic activity expressed as 14C-glucose incorporation into galactogen/microgram DNA and 3H-amino acids into total protein was determined. The glands showed an abrupt decrease in synthetic activity after 1 day of starvation and gradually decreased further until days 9-12. The decrease in activity of the glands was more rapid than that of egg laying. Upon refeeding, the activity of the glands recovered rapidly, simultaneous with the increase in wet weight and egg laying. 4. In conclusion, there is a correlation between egg laying and the in vitro activity of albumen glands. The results show a short-term effect of starvation on the fecundity of the snails. Such studies could be useful in field studies as well as snail control by applying molluscicides under optimal conditions.

Animals↗

Metabolic changes in the African fruit beetle, Pachnoda sinuata, during starvation.

Specimens of the fruit beetle Pachnoda sinuata were starved for up to 30 days. The weight of the beetles declined consistently throughout the starvation period. Concentrations of carbohydrates and alanine in flight muscles, fat body and haemolymph decreased rapidly after onset of starvation, while the concentration of proline remained high. Whereas the lipid concentrations in the haemolymph did not change significantly upon starvation, the lipid content in flight muscles and fat body decreased significantly.Beetles that had been starved for 14 days responded to injection of Mem-CC, the endogenous neuropeptide from its corpora cardiaca, with hyperprolinaemia and a decrease in the alanine level, but no such effect was monitored after prolonged starvation of 28 days. Regardless of the period of starvation, Mem-CC injection could not cause hypertrehalosaemia or hyperlipaemia, although carbohydrates were increased in fed beetles after injection.Flight ability of beetles that had been starved for 15 or 30 days was apparently not impaired. During such periods, beetles used proline exclusively as fuel for flight as evidenced by the increase in the level of alanine in the haemolymph and decrease of the level of proline; the concentrations of carbohydrates and lipids remained unchanged.Activities of malic enzyme and alanine aminotransferase (enzymes involved in transamination in proline metabolism), glyceraldehyde-3-phosphate dehydrogenase (enzyme of glycolysis), 3-hydroxyacyl-CoA dehydrogenase (enzyme of beta-oxidation of fatty acids) and of malate dehydrogenase (enzyme of Krebs cycle) were measured in fat body and flight muscles. In flight muscle tissue the maximum activity of NAD(+)-dependent malic enzyme increased, while that of glyceraldehyde-3-phosphate dehydrogenase decreased during starvation, and malate dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase and alanine aminotransferase were unchanged. In fat body tissue, activities of NADP(+)-dependent malic enzyme and 3-hydroxyacyl-CoA dehydrogenase increased during food deprivation and activities of glyceraldehyde-3-phosphate dehydrogenase, malate dehydrogenase and alanine aminotransferase remained unchanged.

Journal Article↗

High molecular weight water-soluble chitosan protects against apoptosis induced by serum starvation in human astrocytes.

The effect of high molecular weight water-soluble chitosan (WSC) on serum starvation-induced apoptosis in human astrocytes (CCF-STTG1 Cells) was investigated. WSC, having an average molecular weight of 300 kDa and a degree of deacetylation over 90%, can be produced using a simple multi-step membrane separation process. Serum starvation led to growth arrest, rounding up of cells and appearance of p53 bands. Prolonged (48 h) incubation in serum starved medium led to cell detachment and death. WSC significantly protected the serum starvation-induced cellular rounding up and protected the serum starvation-induced cell death as tested by flow cytometry. WSC also protected serum starvation-induced p53 activation as determined by Western blot. These results suggest that WSC may prevent serum starvation-induced apoptosis of CCF-STTG1 cells via p53 inactivation.

Journal Article↗

Exposure to hypoxia, glucose starvation and acidosis: effect on invasive capacity of murine tumor cells and correlation with cathepsin (L + B) secretion.

Cells in tumors may be exposed to adverse conditions such as nutrient deprivation, acidic pH and hypoxia. It has been shown previously that exposure to hypoxia, acidosis and glucose starvation in vitro increases the experimental metastatic ability of murine KHT-LP1 sarcoma, SCC-VII squamous carcinoma and B16 melanoma cells. This effect was most marked when cells were allowed to recover under normal in vitro growth conditions before injection. In the present study we examined whether the invasive capacity of the cells could be influenced by these modifications of the cell microenvironment. We used Matrigel, a basement membrane-like preparation in a two-chamber invasion assay to address this issue. Both KHT-LP1 and SCC-VII murine cell lines showed an increased ability to invade through Matrigel after hypoxia, and glucose starvation, but there was no consistent change in invasive capacity following acidosis exposure. The results for hypoxia and glucose starvation are in agreement with our previous studies of metastatic ability for these cell lines and we confirmed this for KHT-LP1 cells exposed to hypoxia in the current study. In parallel with the invasion assays, we compared cathepsin (L + B) content of the cells in treated and control suspensions. The effect observed varied according to the cell line and the treatment received (hypoxia, glucose starvation). There was an increase of cathepsin content for KHT-LP1 cells exposed to hypoxia and this increase correlated well with the increase of the invasion ability through Matrigel. We did not observe any increase of cathepsin for hypoxia-treated SCC-VII or for KHT-LP1 and SCC-VII cells treated with glucose starvation. These results suggest that transient hypoxia and glucose starvation can increase the invasive ability of tumor cell lines and thus may cause tumor progression by facilitating the invasive step of the metastatic process. The increased levels of cathepsin (L + B) in the KHT-LP1 cells treated with hypoxia, compared to control non-treated cells, may play a part in this increased invasive capacity.

Acidosis↗

Effect of starvation length upon microbial activity in a biomass recycle reactor.

The kinetics of substrate degradation and bacterial growth was determined in a microbial community from a biomass recycle reactor that had been deprived of substrate feed for 0-32 days. Starvation caused changes in bacterial numbers, community composition, and physiological state. Substrate starvation for less than 1 day resulted in modest (less than threefold) changes in endogenous respiration rate, ATP content, and biomass level. During a starvation period of 32 days, there were substantial changes in microbial community composition, as assessed by denaturing gradient gel electrophoresis (DGGE) fingerprinting of PCR amplicons of a portion of the 16S rDNA or by phospholipid fatty acid (PLFA) analysis. When the starved communities were stimulated with organic nutrients, the growth kinetics was a function of the length of the starvation period. For starvation periods of 2-8 days prior to nutrient addition, there was a phase of suboptimal exponential growth (S-phase) in which the exponential growth rate was about 30% of the ultimate unrestricted growth rate. S-phase lasted for 2-8 h and then unrestricted growth occurred at rates of 0.3-0.4 h(-1). At starvation times of 12 and 20 days, a lag phase preceded S-phase and the unrestricted growth phase.

Bacteria↗

Studies in lipogenesis in vivo: Fatty acid and cholesterol synthesis during starvation and re-feeding.

1. Lipogenesis in vivo has been studied in mice given a 250mg. meal of [U-(14)C]glucose (2.5muc) or given an intraperitoneal injection of 25mug. of [U-(14)C]glucose (2.0muc). 2. The ability to convert a [U-(14)C]glucose meal into fatty acid was not significantly depressed by 6-7hr. of starvation. In contrast, incorporation of (14)C into fatty acid in the liver after the intraperitoneal dose of [(14)C]glucose was depressed by 80% and by more than 90% by 1 and 2hr. of starvation respectively. Carcass fatty acid synthesis from the [U-(14)C]glucose meal was not depressed by 12hr. of starvation, whereas from the tracer dose of [U-(14)C]glucose the depression in incorporation was 80% after 6hr. of starvation. 3. Re-feeding for 3 days, after 3 days' starvation, raised fatty acid synthesis and cholesterol synthesis in the liver fivefold and tenfold respectively above the levels in non-starved control mice. These increases were associated with an increased amount of both fatty acid and cholesterol in the liver. 4. After 18hr. of starvation incorporation of a [U-(14)C]glucose meal into carcass and liver glycogen were both increased threefold.

Journal Article↗

Processing of the leader mRNA plays a major role in the induction of thrS expression following threonine starvation in Bacillus subtilis.

The threonyl-tRNA synthetase gene, thrS, is a member of a family of Gram-positive genes that are induced following starvation for the corresponding amino acid by a transcriptional antitermination mechanism involving the cognate uncharged tRNA. Here we show that an additional level of complexity exists in the control of the thrS gene with the mapping of an mRNA processing site just upstream of the transcription terminator in the thrS leader region. The processed RNA is significantly more stable than the full-length transcript. Under nonstarvation conditions, or following starvation for an amino acid other than threonine, the full-length thrS mRNA is more abundant than the processed transcript. However, following starvation for threonine, the thrS mRNA exists primarily in its cleaved form. This can partly be attributed to an increased processing efficiency following threonine starvation, and partly to a further, nonspecific increase in the stability of the processed transcript under starvation conditions. The increased stability of the processed RNA contributes significantly to the levels of functional RNA observed under threonine starvation conditions, previously attributed solely to antitermination. Finally, we show that processing is likely to occur upstream of the terminator in the leader regions of at least four other genes of this family, suggesting a widespread conservation of this phenomenon in their control.

Amino Acyl-tRNA Synthetases↗

Carbohydrate starvation stimulates differential expression of rice alpha-amylase genes that is modulated through complicated transcriptional and posttranscriptional processes.

Expression of alpha-amylase genes in cultured rice suspension cells is induced by sucrose starvation. To study the mechanism of sugar metabolite regulation on the expression of individual alpha-amylase genes, DNA fragments specific to each of eight rice alpha-amylase genes were synthesized and used as gene-specific probes. Comparison of the relative abundance of mRNA revealed that expression of the eight alpha-amylase genes in rice cells was differentially regulated by sucrose starvation. Accumulation of all the alpha-amylase mRNAs increased in response to sucrose starvation; however, levels of the alphaAmy3 and alphaAmy8 mRNAs were distinctly higher and constituted 90% of total alpha-amylase mRNAs. RNA gel blot and nuclear run-on transcription analyses demonstrated a positive correlation between the increased transcription rates and the elevated steady-state levels of alpha-amylase mRNAs induced by sucrose starvation. The half-lives of alphaAmy3, alphaAmy7, and alphaAmy8 were prolonged by sucrose-starvation; however, the stability of the three mRNAs seems controlled by different mechanisms. The translation inhibitors cycloheximide and anisomycin preferentially blocked the sucrose-suppressed expression of alphaAmy3 but not that of alphaAmy7 and alphaAmy8. These inhibitors also enhanced the sucrose starvation-induced accumulation of alphaAmy3 mRNA but not that of alphaAmy7 or alphaAmy8 mRNAs. Cycloheximide did not significantly alter the transcription rates of alpha-amylase genes, suggesting that labile proteins may selectively stabilize the alphaAmy7 and alphaAmy8 mRNAs but destabilize the alphaAmy3 mRNA.

Anisomycin↗

Repression of GCN4 mRNA translation by nitrogen starvation in Saccharomyces cerevisiae.

Saccharomyces cerevisiae activates a regulatory network called "general control" that provides the cell with sufficient amounts of protein precursors during amino acid starvation. We investigated how starvation for nitrogen affects the general control regulatory system, because amino acid biosynthesis is part of nitrogen metabolism. Amino acid limitation results in the synthesis of the central transcription factor Gcn4p, which binds to specific DNA-binding motif sequences called Gcn4-protein-responsive elements (GCREs) that are present in the promoter regions of its target genes. Nitrogen starvation increases GCN4 transcription but efficiently represses expression of both a synthetic GCRE6::lacZ reporter gene and the natural amino acid biosynthetic gene ARO4. Repression of Gcn4p-regulated transcription by nitrogen starvation is independent of the ammonium sensing systems that include Mep2p and Gpa2p or Ure2p and Gln3p but depends on the four upstream open reading frames in the GCN4 mRNA leader sequence. Efficient translation of GCN4 mRNA is completely blocked by nitrogen starvation, even when cells are simultaneously starved for amino acids and eukaryotic initiation factor-2 alpha is fully phosphorylated by Gcn2p. Our data suggest that nitrogen starvation regulates translation of GCN4 by a novel mechanism that involves the four upstream open reading frames but that still acts independently of eukaryotic initiation factor-2 alpha phosphorylation by Gcn2p.

DNA-Binding Proteins↗