Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucose transport in 3T3L1 adipocytes is mediated by two facilitated diffusion transport systems. We examined the effect of chronic glucose deprivation on transport activity and on the expression of the HepG2 (GLUT 1) and adipocyte/muscle (GLUT 4) glucose transporter gene products in this insulin-sensitive cell line. Glucose deprivation resulted in a maximal increase in 2-deoxyglucose uptake of 3.6-fold by 24 h. Transport activity declined thereafter but was still 2.4-fold greater than the control by 72 h. GLUT 1 mRNA and protein increased progressively during starvation to values respectively 2.4- and 7.0-fold greater than the control by 72 h. Much of the increase in total immunoreactive GLUT 1 protein observed later in starvation was the result of the accumulation of a non-functional or mistargeted 38 kDa polypeptide. Immunofluorescence microscopy indicated that increases in GLUT 1 protein occurred in presumptive plasma membrane (PM) and Golgi-like compartments during prolonged starvation. The steady-state level of GLUT 4 protein did not change during 72 h of glucose deprivation despite a greater than 10-fold decrease in the mRNA. Subcellular fractionation experiments indicated that the increased transport activity observed after 24 h of starvation was principally the result of an increase in the 45-50 kDa GLUT 1 transporter protein in the PM. The level of the GLUT 1 transporter in the PM and low-density microsomes (LDM) was increased by 3.9- and 1.4-fold respectively, and the GLUT 4 transporter content of the PM and LDM was 1.7- and 0.6-fold respectively greater than that of the control after 24 h of glucose deprivation. These data indicate that newly synthesized GLUT 1 transporters are selectively shuttled to the PM and that GLUT 4 transporters undergo translocation from an intracellular compartment to the PM during 24 h of glucose starvation. Thus glucose starvation results in an increase in glucose transport in 3T3L1 adipocytes via a complex series of events involving increased biosynthesis, decreased turnover and subcellular redistribution of transporter proteins.
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PMID:Differential regulation of the HepG2 and adipocyte/muscle glucose transporters in 3T3L1 adipocytes. Effect of chronic glucose deprivation. 222 13

Using fusions between the Escherichia coli genes argI and lacZ, it has been demonstrated that ribosomal frameshifting occurs at a frequency of between 3% and 16% within the argI mRNA, soon after the initiation codon. The frameshift involves a phenylalanyl-tRNA shifting into the +1 frame at the sequence UUU-U/C. The shift does not occur if the in-frame phenylalanine codon UUU is replaced by UUC. The level of frameshifting is higher in dense cultures and is not dependent on phenylalanine starvation. In the wild-type argI gene this frameshifting event would be an error, leading to a truncated, non-functional protein. Therefore, it is unlike the numerous examples of required frameshifting events that have been described in other genes.
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PMID:A ribosomal frameshifting error during translation of the argI mRNA of Escherichia coli. 751 62

Multicopy plasmids that have been engineered to produce large quantities of a single gratuitous (non-functional, non-toxic) protein are often problematic. When fully induced, these engineered constructions produce very sick bacteria. The reasons for this may be found in the physiology of wild-type laboratory strains that have been selected to grow at maximum rates with optimal quantities of their proteins. Such bacteria apparently experience the accumulation of gratuitous proteins as an internal shift down and they respond to this with a starvation response. Unlike the shift down associated with a change of growth media, the production of large quantities of gratuitous protein is not associated with a new pre-programmed steady-state of balanced growth. Consequently, the starvation response continues until the bacteria commit suicide by, among other things, destroying their ribosomes.
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PMID:Bacterial growth inhibition by overproduction of protein. 884 28

Mutations in the tumor suppressor p53 are a common event in hepatocellular carcinoma (HCC). Because HCCs typically occur in livers with chronic injury and impaired function, we have explored the role of wild-type p53 in regulating the growth and differentiation of Hep 3B hepatoma cells, a p53-negative line derived from a liver cancer. Stable Hep 3B cell lines were generated in which inducible p53 was introduced using either a temperature-sensitive mutant (p53val135) or a tamoxifen-regulated p53-estrogen receptor chimera (p53-mERtm-pBabepuro). In both cell lines, induction of transcriptionally active p53 was confirmed by assessing several p53 targets: Mdm2 protein, p21waf1 mRNA and protein, and the cyclin G promoter. Despite marked induction of p21waf1, cells with active p53 failed to undergo growth arrest, which is probably due to the presence of a non-functional retinoblastoma protein (pRb) in these cells. Apoptosis also was not observed, even after prolonged (48 h) serum starvation or exposure to cisplatinum. Lack of apoptosis was correlated with unchanged bax mRNA levels following p53 induction. Additionally, albumin mRNA levels remained unchanged, and there was no change in basal transactivation of a reporter containing the promoter of the haptoglobin gene, encoding an acute phase protein. This suggests that growth arrest may be required to promote liver-specific gene expression. Overall, our data demonstrate that introduction of transcriptionally active p53 does not alter the malignant, dedifferentiated phenotype of Hep 3B hepatoma cells. Hence, not all cancer cells are equally responsive to the re-activation of wild-type 53. The ability of a cancer cell to undergo p53-mediated phenotypic alterations may depend on the retention of functional downstream effector pathways.
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PMID:Resistance to p53-mediated growth arrest and apoptosis in Hep 3B hepatoma cells. 923 78

The six biochemical steps of the de novo pyrimidine biosynthesis pathway are conserved in all known organisms. However, in animals and fungi, unlike prokaryotes, at least the first two activities are grouped on a multifunctional enzyme. Here, we report cloning, mapping and transcriptional characterization of some pyrimidine biosynthesis genes in the filamentous fungus Aspergillus nidulans. The first two steps of the pathway are performed by a multifunctional enzyme comprising the activities of carbamoyl phosphate synthetase (CPSase) and aspartate transcarbamylase (ATCase). This polypeptide is encoded by a 7 kbp cluster gene, pyrABCN, which has a high degree of nucleotide identity with the Ura2 gene in Saccharomyces cerevisiae. The enzyme of the third step, dihydroorotase (DHOase), is encoded by a separate locus, pyrD. However, the pyrABCN gene apparently contains an evolutionary remnant of a DHOase-encoding sequence, similarly to the Ura2 gene of Saccharomyces cerevisiae. The pyrABCN gene is transcribed as a single 7 kb mRNA species. The level of transcripts of pyrABCN, pyrD and, to a lesser degree, pyrF genes responds to the presence of exogenous pyrimidines and to the conditions of pyrimidine starvation. Derepression of pyrABCN and pyrD under pyrimidine starvation is noticeably enhanced in pyrE mutants that accumulate dihydroorotic acid. The pyrABCN gene maps to the distal portion of the right arm of the chromosome VIII, whereas the pyrD gene, in contrast to early genetic data, is closely linked to the brlA gene and located to the right of it. Our data on mitotic recombination should help to verify the genetic map of the chromosome VIII. Comparison of amino acid sequences of active dihydroorotases with related enzymes and with their non-functional homologues in yeast and Aspergillus indicates that the active dihydroorotases from fungi are more similar to ureases and enzymes of the pyrimidine degradation pathway. The 'silent' dihydroorotase domains of the multifunctional enzymes from fungi and active DHOase domains of the multifunctional enzymes in higher eukaryotes are more closely related to bacterial dehydroorotases.
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PMID:Structural and transcriptional analysis of the pyrABCN, pyrD and pyrF genes in Aspergillus nidulans and the evolutionary origin of fungal dihydroorotases. 1041 50

Nitrogen starvation and blue light are the two environmental cues that control sexual differentiation in Chlamydomonas reinhardtii. Insertional mutagenesis was applied to generate mutants that still require nitrogen starvation as the initiating signal for gametogenesis but were no longer dependent on irradiation. In one mutant analysed, sequences adjacent to the site of insertion were cloned and used for the isolation of a genomic clone that, upon transformation, could complement the mutant phenotype. The gene identified (LRG6) encodes two mRNAs that appear to be the products of differential splicing. The two putative gene products derived from these mRNAs differ in their C-terminal ends. Both predicted gene products exhibit multiple hydrophobic domains with alpha-helical secondary structure typical for integral membrane proteins. These proteins may form pores, and may function as transporters of as-yet unknown substrates. Since rendering the LRG6 gene non-functional resulted in light-independence of gamete formation, it is suggested that this transporter may inhibit signal flux from the photoreceptor to target genes - either directly by its activity or indirectly by serving as a scaffold for signalling proteins. Shutting off this transporter may be required for the activation of signal flux in this pathway. This concept is supported by the observed reduction in LRG6 mRNA levels during the first phase of gametic differentiation.
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PMID:Knock-out of a putative transporter results in altered blue-light signalling in Chlamydomonas. 1220 48

The stability of p53 tumor suppressor is regulated by Mdm2 via the ubiquitination and proteasome-mediated proteolysis pathway. The c-Abl and PTEN tumor suppressors are known to stabilize p53 by blocking the Mdm2-mediated p53 degradation. This study investigated the correlation between p53 and merlin, a neurofibromatosis 2 (NF2)-related tumor suppressor, in association with the Mdm2 function. The results showed that merlin increased the p53 stability by inhibiting the Mdm2-mediated degradation of p53, which accompanied the increase in the p53-dependent transcriptional activity. The stabilization of p53 by merlin appeared to be accomplished through Mdm2 degradation, and the N-terminal region of merlin was responsible for this novel activity. This study also showed that overexpression of merlin-induced apoptosis of cells depending preferentially on p53 in response to the serum starvation or a chemotherapeutic agent. These results suggest that merlin could be a positive regulator of p53 in terms of tumor suppressor activity, and provide the promising therapeutic means for treating tumors with non-functional merlin or Mdm2 overexpression.
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PMID:Merlin neutralizes the inhibitory effect of Mdm2 on p53. 1467 3

We have identified the Pichia pastoris Vac8 homolog, a 60-64 kDa armadillo repeat protein, and have examined the role of PpVac8 in the degradative pathways involving the yeast vacuole. We report here that PpVac8 is required for glucose-induced pexophagy, but not ethanol-induced pexophagy or starvation-induced autophagy. This has been demonstrated by the persistence of peroxisomal alcohol oxidase activity in mutants lacking PpVac8 during glucose adaptation. During glucose-induced micropexophagy, in the absence of PpVac8, the vacuole was invaginated with arm-like "segmented" extensions that almost completely surrounded the adjacent peroxisomes. Vac8-GFP was found at the vacuolar membrane and concentrated at the base of the arm-like protrusions that extend from the vacuole to sequester the peroxisomes. The localization of Vac8-GFP to the vacuolar membrane occurred independent of PpAtg1, PpAtg9 or PpAtg11. Mutagenesis of the palmitoylated cysteines to alanines or deletion of the myristoylation and palmitoylation sites of PpVac8 resulted in decreased protein stability, impaired vacuolar association and reduced degradation of peroxisomal alcohol oxidase. Deletion of the central armadillo repeat domains of the PpVac8 did not alter its association with the vacuolar membrane, but resulted in a non-functional protein that suppressed the formation of the arm-like extensions from the vacuole to engulf the peroxisomes. PpVac8 is essential for the trafficking of PpAtg11, but not PpAtg1 or PpAtg18, to the vacuole membrane. Together, our results support a role for PpVac8 in early (formation of sequestering membranes) and late (post-MIPA membrane fusion) molecular events of glucose-induced pexophagy.
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PMID:Early and late molecular events of glucose-induced pexophagy in Pichia pastoris require Vac8. 1692 Dec 62

Bacteria respond to nutritional stresses by producing an intracellular alarmone, guanosine 5'-(tri)diphosphate, 3'-diphosphate [(p)ppGpp], which triggers the stringent response resulting in growth arrest and expression of resistance genes. In Escherichia coli, upon fatty acid or carbon starvation, SpoT enzyme activity switches from (p)ppGpp degradation to (p)ppGpp synthesis, but the signal and mechanism for this response remain totally unknown. Here, we characterize for the first time a physical interaction between SpoT and acyl carrier protein (ACP) using affinity co-purifications and two-hybrid in E. coli. ACP, as a central cofactor in fatty acid synthesis, may be an ideal candidate as a mediator signalling starvation to SpoT. Accordingly, we show that the ACP/SpoT interaction is specific of SpoT and ACP functions because ACP does not interact with the homologous RelA protein and because SpoT does not interact with a non-functional ACP. Using truncated SpoT fusion proteins, we demonstrate further that ACP binds the central TGS domain of SpoT, consistent with a role in regulation. The behaviours of SpoT point mutants that do not interact with ACP reveal modifications of the balance between the two opposite SpoT catalytic activities thereby changing (p)ppGpp levels. More importantly, these mutants fail to trigger (p)ppGpp accumulation in response to fatty acid synthesis inhibition, supporting the hypothesis that the ACP/SpoT interaction may be involved in SpoT-dependent stress response. This leads us to propose a model in which ACP carries information describing the status of cellular fatty acid metabolism, which in turn can trigger the conformational switch in SpoT leading to (p)ppGpp accumulation.
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PMID:Acyl carrier protein/SpoT interaction, the switch linking SpoT-dependent stress response to fatty acid metabolism. 1707 15

Differences in the growth of dorsolongitudinal flight muscles and gonads in 1-28 days old long-winged (macropterous) and short-winged (brachypterous) adults of the firebug (Pyrrhocoris apterus L.) and the resource allocation to these organs were studied by means of total protein analysis. We found predominant allocation of food resources to flight muscles compared to reproductive organs in both macropterous males and females during the first 5 days of adult life. Subsequent histolysis of developed flight muscles coincided with increased total protein content in some reproductive organs. Initiation of intensive food intake after starvation or application of higher dose of methoprene on macropterous adults changed the resource allocation in favour of growth of reproductive organs and induced precocious histolysis of flight muscles. It indicates an involvement of juvenile hormone in wing morph-related differential allocation of resources in the bug. Increased total protein contents in the ovaries and accessory glands of starved macropterous females and males treated with methoprene, respectively, indicate that proteins derived from the methoprene-induced histolysis of the flight muscles are re-utilized for the growth of the reproductive organs. It is the first report of persistence of differential resource allocation to flight muscles and reproductive organs in the wing-polymorphic insects with non-functional macropterism.
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PMID:Differential allocation of protein resources to flight muscles and reproductive organs in the flightless wing-polymorphic bug, Pyrrhocoris apterus (L.) (Heteroptera). 1790 60


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