Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0038187 (starvation)
24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stra13 is a transcriptional repressor related within its basic helix-loop-helix domain with the Drosophila Hairy, Enhancer of Split, and the mouse Hes1 proteins that interact with the corepressor Groucho. Because Stra13 lacks the conserved WRPW motif for interaction with Groucho, we examined the function and mechanism of transcriptional repression mediated by Stra13 that exhibits several distinctive features. Here, we report that Stra13 expression is closely associated with cell growth arrest induced by several triggers such as retinoic acid and trichostatin A (TSA; a specific histone deacetylase inhibitor) as well as by serum starvation. Stra13 expression is transcriptionally repressed and maintained at a low level in cells through a negative autoregulatory mechanism that is brought about by its interaction with the corepressor histone deacetylase (HDAC1). This interaction requires the Stra13 C-terminal domain containing three alpha-helices, which are also functionally critical to its repressive activity. Thus, inhibition of HDAC activity by TSA abrogates Stra13-mediated repression of its promoter, resulting in induction of Stra13 expression that is coincident with TSA-induced growth arrest. Further, once induced, Stra13 strongly represses the expression of the cell proliferation-associated gene c-Myc through an HDAC1-independent pathway that involves its interaction with the basal transcription factor TFIIB. Our studies indicate that Stra13 may play a key role in signaling pathways that lead to growth arrest and terminal differentiation by repression of target genes via HDAC-dependent and HDAC-independent mechanisms.
...
PMID:Stra13 expression is associated with growth arrest and represses transcription through histone deacetylase (HDAC)-dependent and HDAC-independent mechanisms. 1073 69

The molecular mechanisms of regulation of the genes involved in the biosynthesis of cysteine are poorly characterized in Bacillus subtilis and other gram-positive bacteria. In this study we describe the expression pattern of the B. subtilis cysH operon in response to sulfur starvation. A 6.1-kb polycistronic transcript which includes the cysH, cysP, ylnB, ylnC, ylnD, ylnE, and ylnF genes was identified. Its synthesis was induced by sulfur limitation and strongly repressed by cysteine. The cysH operon contains a 5' leader portion homologous to that of the S box family of genes involved in sulfur metabolism, which are regulated by a transcription termination control system. Here we show that induction of B. subtilis cysH operon expression is dependent on the promoter and independent of the leader region terminator, indicating that the operon is regulated at the level of transcription initiation rather than controlled at the level of premature termination of transcription. Deletion of a 46-bp region adjacent to the -35 region of the cysH promoter led to high-level expression of the operon, even in the presence of cysteine. We also found that O-acetyl-L-serine (OAS), a direct precursor of cysteine, renders cysH transcription independent of sulfur starvation and insensitive to cysteine repression. We propose that transcription of the cysH operon is negatively regulated by a transcriptional repressor whose activity is controlled by the intracellular levels of OAS. Cysteine is predicted to repress transcription by inhibiting the synthesis of OAS, which would act as an inducer of cysH expression. These novel results provide the first direct evidence that cysteine biosynthesis is controlled at a transcriptional level by both negative and positive effectors in a gram-positive organism.
...
PMID:Transcriptional control of the sulfur-regulated cysH operon, containing genes involved in L-cysteine biosynthesis in Bacillus subtilis. 1100 90

Mad1 is a Myc antagonist that heterodimerizes with Max and functions as a transcriptional repressor. We have studied the effects of Mad1 on cell growth, cell cycle distribution, and apoptosis using Mad1-inducible cell lines. Expression of Mad1 inhibited cell proliferation, S-phase entry, and colony formation, changes that were accompanied by a reduction in CDK2 activity. The inhibition of Mad1 on cell proliferation was potentiated by serum starvation and was paralleled by accumulation of cells in the G0/G1 and the G2 phases of the cell cycle. Mad1 also reduced apoptosis induced by serum withdrawal and by the cytostatic drug cisplatinum. The effects on both cell growth and apoptosis were dependent on the mSin3 interaction domain of Mad1, which is necessary for recruitment of histone deacetylases and corepressors, suggesting that transcriptional repression is mediating these functions. Taken together with the expression pattern of Mad1, these results suggest that Mad1 plays an important role during initiation of differentiation by inhibiting cell proliferation and blocking apoptosis.
...
PMID:Inhibition of cell growth and apoptosis by inducible expression of the transcriptional repressor Mad1. 1101 Aug 11

The Staphylococcus aureus genome encodes three ferric uptake regulator (Fur) homologues: Fur, PerR, and Zur. To determine the exact role of PerR, we inactivated the gene by allelic replacement using a kanamycin cassette, creating strain MJH001 (perR). PerR was found to control transcription of the genes encoding the oxidative stress resistance proteins catalase (KatA), alkyl hydroperoxide reductase (AhpCF), bacterioferritin comigratory protein (Bcp), and thioredoxin reductase (TrxB). Furthermore, PerR regulates transcription of the genes encoding the iron storage proteins ferritin (Ftn) and the ferritin-like Dps homologue, MrgA. Transcription of perR was autoregulated, and PerR repressed transcription of the iron homeostasis regulator Fur, which is a positive regulator of catalase expression. PerR functions as a manganese-dependent, transcriptional repressor of the identified regulon. Elevated iron concentrations produced induction of the PerR regulon. PerR may act as a peroxide sensor, since addition of external hydrogen peroxide to 8325-4 (wild type) resulted in increased transcription of most of the PerR regulon, except for fur and perR itself. The PerR-regulated katA gene encodes the sole catalase of S. aureus, which is an important starvation survival determinant but is surprisingly not required for pathogenicity in a murine skin abscess model of infection. In contrast, PerR is not necessary for starvation survival but is required for full virulence (P < 0.005) in this model of infection. PerR of S. aureus may act as a redox sentinel protein during infection, analogous to the in vitro activities of OxyR and PerR of Escherichia coli and Bacillus subtilis, respectively. However, it differs in its response to the metal balance within the cell and has the added capability of regulating iron uptake and storage.
...
PMID:PerR controls oxidative stress resistance and iron storage proteins and is required for virulence in Staphylococcus aureus. 1134 39

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.
...
PMID:Comparative analysis of idiA and isiA transcription under iron starvation and oxidative stress in Synechococcus elongatus PCC 7942 wild-type and selected mutants. 1460 95

Genes involved in iron (Fe) acquisition often are regulated in response to the local availability of Fe. In many bacteria, Fe-dependent responsiveness is mediated by Fur, a global Fe-dependent transcriptional repressor. Tighter regulatory control of Fur-responsive genes is afforded by incorporating additional regulators into Fur-dependent regulatory cascades. RhuI, a Fur-dependent extracytoplasmic function sigma factor of Bordetella avium, in response to the dual stimulation of Fe starvation and the presence of heme (or hemoproteins), regulates P(bhuR), a heme-responsive promoter which directs expression of the bhuRSTUV heme utilization operon. While BhuR, the outer membrane heme receptor, and RhuI have been shown to be indispensable for heme-dependent activation of P(bhuR), collateral components of the regulatory cascade have not been described. In this investigation, RhuR, an integral cytoplasmic membrane protein with homology to anti-sigma factors, is shown to be an essential activator of P(bhuR) expression. The functional domain of RhuR required for heme-dependent activation of P(bhuR) expression was mapped to the N-terminal 97 amino acids of the protein by use of a chimeric RhuR-BlaM fusion. Expression of the chimera in a rhuR mutant rendered P(bhuR) constitutive, thereby decoupling the promoter from heme dependency. Growth studies confirmed that B. avium requires RhuR for optimal utilization of hemoglobin, but not hemin, as a sole source of nutrient Fe. These data imply that B. avium expresses, in addition to the BhuR heme/hemoprotein utilization system, an alternative RhuR-independent heme utilization mechanism. A model is proposed in which RhuR is the functional bridge between BhuR and RhuI in a heme-dependent regulatory cascade.
...
PMID:RhuR, an extracytoplasmic function sigma factor activator, is essential for heme-dependent expression of the outer membrane heme and hemoprotein receptor of Bordetella avium. 1474 34

The human pathogen Candida albicans grows and colonizes sites that can vary markedly in pH. The pH response in C. albicans is governed in part by the Rim101p pathway. In Saccharomyces cerevisiae, Rim101p promotes alkaline responses by repressing expression of NRG1, itself a transcriptional repressor. Our studies reveal that in C. albicans, Rim101p-mediated alkaline adaptation is not through repression of CaNRG1. Furthermore, our studies suggest that Rim101p and Nrg1p act in parallel pathways to regulate hyphal morphogenesis, an important contributor to virulence. To determine the wild-type C. albicans transcriptional response to acidic and alkaline pH, we utilized microarrays and identified 514 pH-responsive genes. Of these, several genes involved in iron acquisition were upregulated at pH 8, suggesting that alkaline pH induces iron starvation. Microarray analysis of rim101-/- cells indicated that Rim101p does not govern transcriptional responses at acidic pH, but does regulate a subset of transcriptional responses at alkaline pH, including the iron acquisition genes. We found that rim101-/- cells are sensitive to iron starvation, which suggests that one important aspect of the Rim101p-dependent alkaline pH response is to adapt to iron starvation conditions.
...
PMID:Transcriptional profiling in Candida albicans reveals new adaptive responses to extracellular pH and functions for Rim101p. 1555 73

The histone deacetylase Rpd3p functions as a transcriptional repressor of a diverse set of genes, including PHO5. Here we describe a novel role for RPD3 in the regulation of phosphate transporter Pho84p retention in the cytoplasmic membrane. We show that under repressing conditions (with P(i)), PHO5 expression is increased in a pho4Delta rpd3Delta strain, demonstrating PHO regulatory pathway independence. However, the effect of RPD3 disruption on PHO5 activation kinetics is dependent on the PHO regulatory pathway. Upon switching to activating conditions (without P(i)), PHO5 transcripts accumulated more rapidly in rpd3Delta cells. This more rapid response correlates with a defect in phosphate uptake due to premature recycling of Pho84p, the high-affinity H+/PO4(3-) symporter. Thus, RPD3 also participates in PHO5 regulation through a previously unidentified effect on maintenance of high-affinity phosphate uptake during phosphate starvation. We propose that Rpd3p has a negative role in the regulation of Pho84p endocytosis.
...
PMID:Disruption of histone deacetylase gene RPD3 accelerates PHO5 activation kinetics through inappropriate Pho84p recycling. 1608 43

Candida albicans is an opportunistic human pathogen that can sense environmental changes and respond by altering its cell morphology and physiology. A number of environmental factors have been shown to influence this dimorphic transition, including pH, starvation, serum, and amino acids. In this report, we investigate the function of the C. albicans CCAAT-binding factor. In Saccharomyces cerevisiae, this heterooligomeric transcriptional activator stimulates the expression of genes that encode proteins involved in respiration. To examine the function of this transcription factor in C. albicans, we cloned CaHAP5 and generated a hap5delta/hap5delta mutant of C. albicans. Using mobility shift studies, we identified four separate complexes from C. albicans cell extracts whose DNA-binding activities were abolished in the hap5delta/hap5delta mutant, suggesting that they represented sequence-specific CCAAT-binding complexes. We found that the C. albicans hap5delta homozygote was defective in hyphal development under a variety of conditions, and the mutant displayed a carbon source-dependent "hyperfilamentation" phenotype under certain growth conditions. In addition, the mRNA levels for two enzymes involved in respiration, encoded by COX5 and CYC1, were overexpressed in the hap5delta/hap5delta mutant when grown in medium containing amino acids as the sole carbon and nitrogen source. Thus, the C. albicans CCAAT-binding factor appeared to function as a repressor of genes encoding mitochondrial electron transport components, in contrast to its activator function in S. cerevisiae. These data provide the first evidence that the CCAAT-binding factor can act as a transcriptional repressor and raise new and interesting questions about how carbon metabolism is regulated in this opportunistic human pathogen.
...
PMID:Novel regulatory function for the CCAAT-binding factor in Candida albicans. 1621 74

Recent advanced studies of genomics and proteomics have revealed the variation and diversity of ribosomal proteins (r-proteins) in different organisms and organelles. Radical free and highly reducing (RFHR) two-dimensional (2-D) electrophoresis is known to be powerful for separating ribosomal proteins that are usually small and basic, and not separated well by standard 2-D electrophoresis. Using the RFHR method, we investigated the protein profile of the Bacillus subtilis ribosomes by a proteomic approach. We found that two L31 paralogue proteins (RpmE and YtiA) showed different temporal expression patterns in the ribosomes. The RpmE protein, which is an L31 variant with a Zn-binding motif, binds one zinc ion at the motif, which is required for stabilization of the protein in the cell. On the other hand, the expression of the ytiA gene, which encodes another L31 variant (YtiA) without the Zn-binding motif, is negatively controlled by the zinc-specific transcriptional repressor Zur and is likely induced by zinc starvation. This article reviews the recent findings that replacement of two types of L31 proteins in the ribosome is controlled by the intracellular zinc concentration.
...
PMID:Proteomic study of the Bacillus subtilis ribosome: Finding of zinc-dependent replacement for ribosomal protein L31 paralogues. 1731 68


<< Previous 1 2 3 4 Next >>

---