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

The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK). To identify transcriptional regulators acting downstream from or in parallel to PKA, we screened an adh-driven cDNA plasmid library for genes that increase fbp1 transcription in a strain with elevated PKA activity. Two such clones express amino-terminally truncated forms of the S. pombe tup12 protein that resembles the Saccharomyces cerevisiae Tup1p global corepressor. These clones appear to act as dominant negative alleles. Deletion of both tup12 and the closely related tup11 gene causes a 100-fold increase in fbp1-lacZ expression, indicating that tup11 and tup12 are redundant negative regulators of fbp1 transcription. In strains lacking tup11 and tup12, the atf1-pcr1 transcriptional activator continues to play a central role in fbp1-lacZ expression; however, spc1 MAPK phosphorylation of atf1 is no longer essential for its activation. We discuss possible models for the role of tup11- and tup12-mediated repression with respect to signaling from the MAPK and PKA pathways. A third clone identified in our screen expresses the php5 protein subunit of the CCAAT-binding factor (CBF). Deletion of php5 reduces fbp1 expression under both repressed and derepressed conditions. The CBF appears to act in parallel to atf1-pcr1, although it is unclear whether or not CBF activity is regulated by PKA.
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PMID:Transcriptional regulators of the Schizosaccharomyces pombe fbp1 gene include two redundant Tup1p-like corepressors and the CCAAT binding factor activation complex. 1123 5

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.
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PMID:Novel regulatory function for the CCAAT-binding factor in Candida albicans. 1621 74

The fission yeast Schizosaccharomyces pombe responds to the deprivation of iron by inducing the expression of the php4+ gene, which encodes a negative regulatory subunit of the heteromeric CCAAT-binding factor. Once formed, the Php2/3/4/5 transcription complex is required to inactivate a subset of genes encoding iron-using proteins. Here, we used a pan-S. pombe microarray to study the transcriptional response to iron starvation and identified 86 genes that exhibit php4+-dependent changes on a genome-wide scale. One of these genes encodes the iron-responsive transcriptional repressor Fep1, whose mRNA levels were decreased after treatment with the permeant iron chelator 2,2'-dipyridyl. In addition, several genes encoding the components of iron-dependent biochemical pathways, including the tricarboxylic acid cycle, mitochondrial respiration, amino acid biosynthesis, and oxidative stress defense, were downregulated in response to iron deficiency. Furthermore, Php4 repressed transcription when brought to a promoter using a yeast DNA-binding domain, and iron deprivation was required for this repression. On the other hand, Php4 was constitutively active when glutathione levels were depleted within the cell. Based on these and previous results, we propose that iron-dependent inactivation of Php4 is regulated at two distinct levels: first, at the transcriptional level by the iron-responsive GATA factor Fep1 and second, at the posttranscriptional level by a mechanism yet to be identified, which inhibits Php4-mediated repressive function when iron is abundant.
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PMID:Key function for the CCAAT-binding factor Php4 to regulate gene expression in response to iron deficiency in fission yeast. 1822 16

In Schizosaccharomyces pombe, the iron sensor Fep1 mediates the transcriptional repression of iron transport genes in response to high concentrations of iron. On the other hand, fep1(+) expression is downregulated under conditions of iron starvation by the CCAAT-binding factor Php4. In this study, we created a fep1Delta php4Delta double mutant strain where expression of fep1(+) was disengaged from its iron limitation-dependent repression by Php4 to examine the effects of iron on constitutively expressed functional fep1(+)-GFP and TAP-fep1(+) alleles and their gene products. In these cells, Fep1-green fluorescent protein was invariably localized in the nucleus under both iron-limiting and iron-replete conditions. Using chromatin immunoprecipitation assays, we found that Fep1 is associated with iron-responsive promoters in vivo. Chromatin binding was iron dependent, with a loss of binding observed in the presence of low iron. Functional dissection of the protein revealed that the N-terminal 241-residue segment that includes two consensus Cys(2)/Cys(2)-type zinc finger motifs and a Cys-rich region is required for optimal promoter occupancy by Fep1. Within this segment, a minimal module encompassing amino acids 60 to 241 is sufficient for iron-dependent chromatin binding. Using yeast one-hybrid analysis, we showed that the replacement of the repression domain of Fep1 by fusing the activation domain of VP16 to the chromatin-binding fragment of amino acids 1 to 241 of Fep1 converts the protein from an iron-dependent repressor into an iron-dependent transcriptional activator. Thus, the repression function of Fep1 can be replaced with that of a transcriptional activation function without the loss of its iron-dependent DNA-binding activity.
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PMID:Iron activates in vivo DNA binding of Schizosaccharomyces pombe transcription factor Fep1 through its amino-terminal region. 1925 22

In Schizosaccharomyces pombe, the CCAAT-binding factor is a multisubunit complex that contains the proteins Php2, Php3, Php4, and Php5. Under low iron conditions, Php4 acts as a negative regulatory subunit of the CCAAT-binding factor and fosters repression of genes encoding iron-using proteins. Under conditions of iron excess, Php4 expression is turned off by the iron-dependent transcriptional repressor Fep1. In this study, we developed a biological system that allows us to unlink iron-dependent behavior of Php4 protein from its transcriptional regulation by Fep1. Microscopic analyses revealed that a functional GFP-Php4 protein accumulates in the nucleus under conditions of iron starvation. Conversely, in cells undergoing a transition from low to high iron, GFP-Php4 is exported from the nucleus to the cytoplasm. We mapped a leucine-rich nuclear export signal that is necessary for nuclear exclusion of Php4. This latter process was blocked by leptomycin B. By using coimmunoprecipitation analysis, we showed that Php4 and Crm1 physically interact with each other. Although we determined that nuclear retention of Php4 per se is not sufficient to cause a constitutive repression of iron-using genes, we found that deletion of the grx4(+)-encoded glutaredoxin-4 renders Php4 constitutively active and invariably localized in the nucleus. Further analysis by bimolecular fluorescence complementation assay and by two-hybrid assays showed that Php4 and Grx4 are physically associated in vivo. Taken together, our findings indicate that Grx4 and Crm1 are novel components involved in the mechanism by which Php4 is inactivated by iron in a Fep1-independent manner.
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PMID:Both Php4 function and subcellular localization are regulated by iron via a multistep mechanism involving the glutaredoxin Grx4 and the exportin Crm1. 1950 36

When iron load exceeds that needed by fission and filamentous yeasts, iron-regulatory GATA-type transcription factors repress genes encoding iron acquisition systems. In contrast, under iron starvation, optimization of cellular iron utilization is coordinated by a specialized regulatory subunit of the CCAAT-binding factor that fosters repression of genes encoding iron-using proteins. Despite these findings, there is still limited knowledge concerning the mechanisms by which these iron-responsive regulators respond to high- or low-iron availability. To provide a framework for understanding common and distinct properties of iron-dependent transcriptional regulators, a repertoire of their functional domains in different fungal species is presented here. In addition, discovery of interacting partners of these iron-responsive factors contributes to provide additional insight into their properties.
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PMID:Molecular basis of the regulation of iron homeostasis in fission and filamentous yeasts. 2647 34