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

Protein prenylation is a posttranslational modification involving the covalent attachment of a prenyl lipid to a cysteine at or near the COOH terminus of a protein. It is required for membrane localization and efficient function of a number of cytoplasmic as well as nuclear proteins including the proto-oncogenic and activated forms of Ras. Farnesylation in conjunction with a nuclear localization signal has been shown to be necessary to target newly synthesized nuclear lamins to the inner nuclear envelope membrane. It is, however, not clear where in the cell isoprenylation of nuclear lamins takes place. In this study we describe in vivo and in vitro experiments on the isoprenylation of the Xenopus oocyte nuclear lamin B3. We show by kinetic analysis that newly synthesized lamins are isoprenylated in the cytosol of oocytes before uptake into the nucleus. From our data it can be concluded that isoprenylation of lamins in the nucleus, as it is observed under certain conditions of isoprene starvation, represents a default pathway rather than the physiological situation. We further analyzed the capacity of isolated nuclei to carry out isoprenylation of B3. Our results are in line with a dual localization of a protein farnesyltransferase in the cytosol and nuclei of amphibian oocytes. Implications for the possible functions of a nuclear protein farnesyltransferase as well as possible mechanisms of the selective inhibition of farnesylation of cytoplasmic proteins by peptidomimetics are discussed.
 ...
PMID:Analysis of nuclear lamin isoprenylation in Xenopus oocytes: isoprenylation of lamin B3 precedes its uptake into the nucleus. 769 83

Metallothioneins constitute a class of low-molecular-weight, cysteine-rich metal-binding stress proteins which are biosynthetically regulated at the level of gene transcription in response to metals, hormones, cytokines, and other physiological and environmental stresses. In this report, we demonstrate that the Saccharomyces cerevisiae metallothionein gene, designated CUP1, is transcriptionally activated in response to heat shock and glucose starvation through the action of heat shock transcription factor (HSF) and a heat shock element located within the CUP1 promoter upstream regulatory region. CUP1 gene activation in response to both stresses occurs rapidly; however, heat shock activates CUP1 gene expression transiently, whereas glucose starvation activates CUP1 gene expression in a sustained manner for at least 2.5 h. Although a carboxyl-terminal HSF transcriptional activation domain is critical for the activation of CUP1 transcription in response to both heat shock stress and glucose starvation, this region is dispensable for transient heat shock activation of at least two genes encoding members of the S. cerevisiae hsp70 family. Furthermore, inactivation of the chromosomal SNF1 gene, encoding a serine-threonine protein kinase, or the SNF4 gene, encoding a SNF1 cofactor, abolishes CUP1 transcriptional activation in response to glucose starvation without altering heat shock-induced transcription. These studies demonstrate that the S. cerevisiae HSF responds to multiple, distinct stimuli to activate yeast metallothionein gene transcription and that these stimuli elicit responses through nonidentical, genetically separable signalling pathways.
 ...
PMID:Heat shock transcription factor activates yeast metallothionein gene expression in response to heat and glucose starvation via distinct signalling pathways. 796 52

Casein kinase II of Saccharomyces cerevisiae is composed of two distinct catalytic subunits, alpha and alpha', and two distinct regulatory subunits, beta and beta' (Padmanabha, R. and Glover, C. V. C. (1987) J. Biol. Chem. 262, 1829-1835; Bidwai, A. P., Reed, J. C., and Glover, C. V. C. (1994) Arch. Biochem. Biophys. 309, 348-355). We report here the cloning, sequencing, and disruption of the CKB2 gene encoding the beta'-subunit. The deduced amino acid sequence of Ckb2 displays only 40-45% identity to other beta-subunit sequences reported to date, allowing a better definition of conserved features of this protein. Most notable is the conservation of a cysteine-containing sequence, CPX3C-X22-CPXC, which may constitute a novel metal-binding motif. The degree of sequence divergence of Ckb2 is comparable to that of the Drosophila Stellate protein, a testis-specific protein of unknown function, suggesting that the latter may function as a second beta-subunit in Drosophila. CKB2 is located on the right arm of chromosome XV between the HIR2 and WHI2 loci and has not been previously identified genetically. Haploid and homozygous diploid cells harboring a ckb2 null allele are viable, demonstrating that the beta'-subunit does not have an essential function distinct from that of beta. Strains lacking a functional CKB2 gene appear to grow normally on both fermentable and non-fermentable carbon sources, mate and sporulate normally, and display normal resistance to nitrogen starvation and heat shock. However, haploid strains harboring disruptions of both the beta' gene and either of the catalytic subunit genes exhibit a synthetic phenotype consisting of slow growth and flocculation in rich glucose medium. The occurrence of this synthetic phenotype implies that the beta'-subunit interacts physically and/or functionally with both the alpha- and alpha'-subunits in vivo.
 ...
PMID:Cloning and disruption of CKB2, the gene encoding the 32-kDa regulatory beta'-subunit of Saccharomyces cerevisiae casein kinase II. 802 80

Two-dimensional gel electrophoresis of proteins from Escherichia coli, Pseudomonas putida, and Staphylococcus aureus, grown with methionine or one of a variety of organosulfates and organosulfonates as the sole source of sulfur, showed expression of specific sets of 7 to 14 proteins which were not observed during growth with sulfate or cysteine for all three species or with thiocyanate for P. putida and S. aureus. Under the same conditions, arylsulfatase activity in P. putida and S. aureus was seen to increase by up to 140-fold, suggesting that the proteins induced under these conditions may be involved in sulfur metabolism. We propose that these proteins are members of a sulfate starvation-induced stimulon.
 ...
PMID:Proteins induced by sulfate limitation in Escherichia coli, Pseudomonas putida, or Staphylococcus aureus. 843 11

A temperature-sensitive methionine auxotroph of Neurospora crassa was found in a collection of conditional mutants and shown to be deficient in DNA methylation when grown under semipermissive conditions. The defective gene was identified as met-3, which encodes cystathionine-gamma-synthase. We explored the possibility that the methylation defect results from deficiency of S-adenosylmethionine (SAM), the presumptive methyl group donor. Methionine starvation of mutants from each of nine complementation groups in the methionine (met) pathway (met-1, met-2, met-3, met-5, met-6, met-8, met-9, met-10 and for) resulted in decreased DNA methylation while amino acid starvation, per se, did not. In most of the strains, including wild-type, intracellular SAM peaked during rapid growth (12-18 h after inoculation), whereas DNA methylation continued to increase. In met mutants starved for methionine, SAM levels were most reduced (3-11-fold) during rapid growth while the greatest reduction in DNA methylation levels occurred later. Addition of 3 mM methionine to cultures of met or cysteine-requiring (cys) mutants resulted in 5-28-fold increases in SAM, compared with wild-type, at a time when DNA methylation was reduced approximately 40%, suggesting that the decreased methylation during rapid growth in Neurospora is not due to limiting SAM. DNA methylation continued to increase in a cys-3 mutant that had stopped growing due to methionine starvation, suggesting that methylation is not obligatorily coupled to DNA replication in Neurospora.
 ...
PMID:Mutations affecting the biosynthesis of S-adenosylmethionine cause reduction of DNA methylation in Neurospora crassa. 853 24

Neisseria meningitidis strains grown under iron starvation conditions produce transferrin binding proteins (Tbp1 and Tbp2) which have been shown to play a major role in iron acquisition. Recent studies performed with Tbp2 purified from N. meningitidis suggest that this surface protein is a potential vaccine component. In order to further evaluate the immunogenicity of Tbp2, it was essential to develop a heterologous expression system to generate high amounts of purified protein. Tbp2 is produced in Neisseria as a precursor with a signal peptide whose cleavage follows a lipidation step on a cysteine residue which is the first amino acid in the mature protein. When produced in Escherichia coli with its natural signal peptide, a high amount of Tbp2 (about 10% of total cell proteins) was detected. However, most of the protein was nonlipidated precursor and only a small fraction was mature Tbp2. In order to optimize the maturation of the precursor, the natural signal sequence was replaced by several E. coli lipoprotein signal peptides. Expression levels and maturation of the precursor were highly variable depending on the signal peptide used. With one of these, an efficient maturation and a high amount of mature lipidated Tbp2 were obtained (about 3% of total cell proteins). A large-scale production process was then established for this E. coli-produced Tbp2.
 ...
PMID:Production of lipidated meningococcal transferrin binding protein 2 in Escherichia coli. 853 48

The adaptive response of the archaeon Sulfolobus acidocaldarius BC65 to phosphate starvation was studied. When cells were subjected to phosphate limitation, their growth was affected. In addition, the levels of synthesis and/or the degree of phosphorylation of several proteins changed, as detected by two-dimensional nonequilibrium pH gradient electrophoresis of cells labelled in vivo with [35S]methionine and [35S]cysteine, or H3 32PO4. After another growth-restricting treatment, a heat shock, a general inhibition of protein synthesis was observed. Under phosphate starvation conditions, a 36 kDa protein became phosphorylated without its synthesis being significantly modified, suggesting a probable regulatory role during adaptation of the cell to the change in the external environment. In Southern blot analysis with specific probes from very conserved regions of the phoR and phoB genes from Escherichia coli, a positive hybridization with S. acidocaldarius BC65 chromosomal DNA fragments was found. This suggested the presence in S. acidocaldarius BC65 of genes related to the E. coli genes involved in the phosphate starvation response system. This appears to be the first evidence of the possible existence of a two-component sensory system in a micro-organism from the archaeal kingdom Crenarchaeota.
 ...
PMID:Adaptive response of the archaeon Sulfolobus acidocaldarius BC65 to phosphate starvation. 870 93

Proper bodily response to environmental toxicants presumably requires proper function of the xenobiotic (foreign chemical) detoxification pathways. Links between phenotypic variations in xenobiotic metabolism and adverse environmental response have long been sought. Metabolism of the drug S-carboxymethyl-L-cysteine (SCMC) is polymorphous in the population, having a bimodal distribution of metabolites, 2.5% of the general population are thought to be nonmetabolizers. The researchers developing this data feel this implies a polymorphism in sulfoxidation of the amino acid cysteine to sulfate. While this interpretation is somewhat controversial, these metabolic differences reflected may have significant effects. Additionally, a significant number of individuals with environmental intolerance or chronic disease have impaired sulfation of phenolic xenobiotics. This impairment is demonstrated with the probe drug acetaminophen and is presumably due to starvation of the sulfotransferases for sulfate substrate. Reduced metabolism of SCMC has been found with increased frequency in individuals with several degenerative neurological and immunological conditions and drug intolerances, including Alzheimer's disease, Parkinson's disease, motor neuron disease, rheumatoid arthritis, and delayed food sensitivity. Impaired sulfation has been found in many of these conditions, and preliminary data suggests that it may be important in multiple chemical sensitivities and diet responsive autism. In addition, impaired sulfation may be relevant to intolerance of phenol, tyramine, and phenylic food constituents, and it may be a factor in the success of the Feingold diet. These studies indicate the need for the development of genetic and functional tests of xenobiotic metabolism as tools for further research in epidemiology and risk assessment.
 ...
PMID:Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways. 871 48

The trace element copper (Cu) is essential for cell growth. In this report we describe the identification of a new component of the high-affinity Cu transport machinery in yeast, encoded by the CTR3 gene. Ctr3p is a small intracellular cysteine-rich integral membrane protein that restores high-affinity Cu uptake, Cu, Zn superoxide dismutase activity, ferrous iron transport, and respiratory proficiency to strains lacking the CTR1 (Cu transporter 1) gene. In most commonly used Saccharomyces cerevisiae laboratory strains, expression of CTR3 is abolished by a Ty2 transposon insertion that separates the CTR3 promoter from the transcriptional start sites by 6 kb. In strains that do not possess a Ty2 transposon at the CTR3 locus, expression of CTR3 is repressed by copper and activated by copper starvation. In such strains inactivation of both CTR1 and CTR3 is required to generate lethal copper-deficient phenotypes. Although Ctr1p and Ctr3p can function independently in copper transport, the expression of both proteins provides maximal copper uptake and growth rate under copper-limiting conditions. These results underscore the importance of mobile DNA elements in the alteration of gene function and phenotypic variation.
 ...
PMID:A widespread transposable element masks expression of a yeast copper transport gene. 875 49

A set of 8 proteins (SSI, sulfate-starvation-induced proteins) was observed by comparative two-dimensional electrophoresis to be induced when Escherichia coli were grown using compounds other than sulfate or cysteine as the sole sulfur source. These proteins were isolated after two-dimensional gel electrophoresis, digested with trypsin and the masses of the resulting peptides determined by mass spectrometry. The list of peptide masses served as a protein fingerprint which was used to search the databases, allowing four of the SSI proteins (SSI2, 5, 7, 8) to be identified with a high degree of confidence. To identify the other SSI proteins, and to obtain sequence information for as many of the proteins as possible, automated on-line HPLC MS/MS (fragmentation analysis using coupled mass scanning devices) data collection was performed. The uninterpreted MS/MS spectra were used as peptide fingerprints to search the databases. Genes encoding two further proteins (SSI 1 and 3) were identified in the 8.5' region of the Escherichia coli genome. N-terminal sequencing of all of the proteins confirmed the results of protein and peptide fingerprinting and in addition showed that SSI 6 shows 50% similarity to the Bacillus subtilis orfM gene product. SSI 4 was not found in the databases by any of these methods. The methods described are of general use for the rapid analysis of complex cell responses. MS data accumulation takes about 5 min/protein for protein fingerprinting and 30 min for peptide fingerprinting and requires approximately 100 fmol of material. N-terminal sequencing however, takes about 5 h/protein and approximately 1 pmol to obtain a 10 amino acid sequence for a search.
 ...
PMID:Analysis of global responses by protein and peptide fingerprinting of proteins isolated by two-dimensional gel electrophoresis. Application to the sulfate-starvation response of Escherichia coli. 877 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>