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)

Alkalization of the medium is associated with and required for the cellular development to meiosis and sporulation in the yeast Saccharomyces cerevisiae. To elucidate the molecular mechanisms for the significance of external alkalization, we isolated mutants defective in division arrest at G1 phase under an alkaline condition. The mutants obtained had recessive alleles of SRB10 encoding the cyclin (SRB11)-dependent protein kinase that phosphorylates the CTD domain of the largest subunit of RNA polymerase II and negatively regulates the transcriptional initiation of certain genes. A delta srb11 deletion mutant showed the same cell cycle defect. When shifted to alkali, wild-type cells decreased transcript levels of G1-cyclin genes (CLN1 to CLN3) and KIN28-CCL1 (encoding another CTD kinase-cyclin pair which, in contrast, stimulates the promoter clearance and transcriptional elongation in most genes), resulting in the accumulation of G1 cells and the hypophosphorylated form of RNA polymerase II and in an increase in cell size. However, under the same conditions, a delta srb10 mutant was defective in these events, except the downregulation of CLN1 and CLN2. The delta srb10 mutation also influenced on the transcript levels of meiosis-inducing genes called IME1 and IME2: the mutation elevated the transcript level of IME1 but reduced that of IME2, resulting in partial defects in premeiotic DNA synthesis and meiosis. Overexpression of KIN28 and CCL1 in wild-type cells impaired the alkali-induced G1 arrest and the rate of meiosis and elevated the transcript levels of SRB11 and IME1. These results indicate that a transcriptional autoregulatory loop for KIN28-CCL1 and SRB10-SRB11 is important for G1 arrest and meiosis. We also found that environmental conditions for meiosis finely regulate the transcript levels of KIN28 and CCL1, such that nitrogen starvation first elevates them but subsequent alkalization of medium decreases them.
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PMID:A transcriptional autoregulatory loop for KIN28-CCL1 and SRB10-SRB11, each encoding RNA polymerase II CTD kinase-cyclin pair, stimulates the meiotic development of S. cerevisiae. 1086 6

Saccharomyces cerevisiae cells enter into a distinct resting state, known as stationary phase, in response to specific types of nutrient deprivation. We have identified a collection of mutants that exhibited a defective transcriptional response to nutrient limitation and failed to enter into a normal stationary phase. These rye mutants were isolated on the basis of defects in the regulation of YGP1 expression. In wild-type cells, YGP1 levels increased during the growth arrest caused by nutrient deprivation or inactivation of the Ras signaling pathway. In contrast, the levels of YGP1 and related genes were significantly elevated in the rye mutants during log phase growth. The rye defects were not specific to this YGP1 response as these mutants also exhibited multiple defects in stationary phase properties, including an inability to survive periods of prolonged starvation. These data indicated that the RYE genes might encode important regulators of yeast cell growth. Interestingly, three of the RYE genes encoded the Ssn/Srb proteins, Srb9p, Srb10p, and Srb11p, which are associated with the RNA polymerase II holoenzyme. Thus, the RNA polymerase II holoenzyme may be a target of the signaling pathways responsible for coordinating yeast cell growth with nutrient availability.
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PMID:The rye mutants identify a role for Ssn/Srb proteins of the RNA polymerase II holoenzyme during stationary phase entry in Saccharomyces cerevisiae. 1113 88

Organisms respond to environmental stress by adopting changes in gene expression at the transcriptional level. Rpb4, a nonessential subunit of the core RNA polymerase II has been proposed to play a role in non-stress-specific transcription and in the regulation of stress response in yeast. We find that in addition to the temperature sensitivity of the null mutant of Rpb4, diploid null mutants are also compromised in sporulation and show morphological changes associated with nitrogen starvation. Using whole genome expression analysis, we report here the effects of Rpb4 on expression of genes during normal growth and following heat shock and nutritional starvation. Our analysis shows that Rpb4 affects expression of a small yet significant fraction of the genome in both stress and normal conditions. We found that genes involved in galactose metabolism were dependent on the presence of Rpb4 irrespective of the environmental condition. Rpb4 was also found to affect the expression of several other genes specifically in conditions of nutritional starvation. The general defect in the absence of Rpb4 is in the expression of metabolic genes, especially those involved in carbon metabolism and energy generation. We report that various stresses are affected by RPB4 and that on overexpression the stress-specific activators can partially rescue the corresponding defects.
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PMID:Whole genome expression profiles of yeast RNA polymerase II core subunit, Rpb4, in stress and nonstress conditions. 1242 47

When mammalian cells are exposed to cisplatin or ultraviolet irradiation, the RNA polymerase II (RNAP II) large subunit becomes ubiquitinated and is subsequently degraded via the proteasomal pathway. Using a DNA template immobilized on magnetic beads in an in vitro transcription reaction, we showed that a pause of the elongating RNAP II complex caused by nucleotide starvation induced the ubiquitination of the stalled RNAP II. The ubiquitinated RNAP II dissociated from the ternary complex when transcription was allowed to resume. The dissociated (free) RNAP II remained ubiquitinated. The proteasome inhibitor MG132 increased the accumulation of ubiquitinated free RNAP II but did not affect the amount of ubiquitinated, template-bound RNAP II, indicating that the ubiquitinated RNAP II was displaced from the template and then degraded by the proteasomes. Our work shows that the elongation complex that was stalled at the template by nucleotide starvation is targeted by the ubiquitin-conjugating system and that ubiquitination facilitates displacement of the stalled RNAP II from the template. Our findings together with the findings by others that DNA damaging agents induced the ubiquitination in mammalian cells that are nucleotide excision repair competent, suggest that the RNAP II ubiquitination may have a role in the regulation of transcription-coupled DNA repair.
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PMID:RNA polymerase II stalled on a DNA template during transcription elongation is ubiquitinated and the ubiquitination facilitates displacement of the elongation complex. 1257 24

White-rot fungus Phanerochaete chrysosporium, a ligninolytic basidiomycete, was studied to identify iron-responsive genes. Using the differential display reverse transcription PCR technique (DDRT-PCR), a total of 97 differentially expressed cDNA fragments were identified by comparing band intensities among fingerprints obtained from mycelia cultivated in iron-deficient and iron-replete media. Transcripts induced under iron-starvation exhibited homologies to: a modular polyketide synthase, a TonB protein, a probable transmembrane protein, a putative ABC transporter permease and a HSP70-related heat-shock protein. Modular polyketide synthase and TonB proteins are normally expressed under iron-starvation and are known to be involved in biosynthesis and transport of siderophores respectively. Also, a deduced protein with 96% similarity to a precursor of the well-known P. chrysosporium lignin peroxidase was identified under iron-deficiency. Two DDRT-PCR products confirmed their iron-induced expression. One was homologue to the CNOT3, which is a global regulator of RNA polymerase II transcription and has been implicated in multiple roles in the control of mRNA metabolism. The other was similar to the Schizosaccharomyces pombe putative proteasome maturation factor upm1. In conclusion, the majority of iron-responsive P. chrysosporium transcripts isolated in the DDRT-PCR encode proteins involved in iron acquisition, especially members of biosynthesis and transport of iron chelators.
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PMID:Iron-responsive genes of Phanerochaete chrysosporium isolated by differential display reverse transcription polymerase chain reaction. 1291 13

To identify genetic factors contributing to psoriasis susceptibility, gene expression profiles of uninvolved epidermis from psoriatic patients and epidermis from healthy individuals were compared. Besides already characterized genes, we identified a cDNA with yet unknown functions, which we further characterized and named PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). In silico structural and homology studies suggested that PRINS may function as a noncoding RNA. PRINS harbors two Alu elements, it is transcribed by RNA polymerase II, and it is expressed at different levels in various human tissues. Real time reverse transcription-PCR analysis showed that PRINS was expressed higher in the uninvolved epidermis of psoriatic patients compared with both psoriatic lesional and healthy epidermis, suggesting a role for PRINS in psoriasis susceptibility. PRINS is regulated by the proliferation and differentiation state of keratinocytes. Treatment with T-lymphokines, known to precipitate psoriatic symptoms, decreased PRINS expression in the uninvolved psoriatic but not in healthy epidermis. Real time reverse transcription-PCR analysis showed that stress signals such as ultraviolet-B irradiation, viral infection (herpes simplex virus), and translational inhibition increased the RNA level of PRINS. Gene-specific silencing of PRINS by RNA interference revealed that down-regulation of PRINS impairs cell viability after serum starvation but not under normal serum conditions. Our findings suggest that PRINS functions as a noncoding regulatory RNA, playing a protective role in cells exposed to stress. Furthermore, elevated PRINS expression in the epidermis may contribute to psoriasis susceptibility.
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PMID:Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS. 1585 53

Rpb4p and Rpb7p are subunits of the RNA polymerase II of Saccharomyces cerevisiae that form a dissociable heterodimeric complex. Whereas the only reported function of Rpb7p is related to transcription, Rpb4p has been found to also act in mRNA export and in the major mRNA decay pathway that operates in the cytoplasm, thus raising the possibility that Rpb4p links between the nuclear and cytoplasmic processes. Here we show that both Rpb4p and Rpb7p shuttle between the nucleus and the cytoplasm. Shuttling kinetics of the two proteins are similar as long as their interaction is possible, suggesting that they shuttle as a heterodimer. Under normal conditions, shuttling of Rpb4p and Rpb7p depends on ongoing transcription. However, during severe stresses of heat shock, ethanol, and starvation, the two proteins shuttle via a transcription-independent pathway. Thus, Rpb4p and Rpb7p shuttle via two pathways, depending on environmental conditions.
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PMID:Nucleocytoplasmic shuttling of the Rpb4p and Rpb7p subunits of Saccharomyces cerevisiae RNA polymerase II by two pathways. 1705 45

The Rpb4/7 subcomplex of RNA polymerase II in Saccharomyces cerevisiae is known to play an important role in stress response and stress survival. These two proteins perform overlapping functions ensuring an appropriate cellular response through transcriptional regulation of gene expression. Rpb4 and Rpb7 also perform many cellular functions either together or independent of one another. Here, we show that Rpb4 and Rpb7 differently affect during the nutritional starvation response pathways of sporulation and pseudohyphae formation. Rpb4 enhances the cells' proficiency to sporulate but suppresses pseudohyphal growth. On the other hand, Rpb7 promotes pseudohyphal growth and suppresses sporulation in a dose-dependent manner. We present a model whereby the stoichiometry of Rpb4 and Rpb7 and their relative levels in the cell play a switch like role in establishing either sporulation or pseudohyphal gene expression.
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PMID:Relative levels of RNA polII subunits differentially affect starvation response in budding yeast. 1734 70

Body cells in multicellular organisms are in the G0 state, in which cells are arrested and terminally differentiated. To understand how the G0 state is maintained, the genes that are specifically expressed or repressed in G0 must be identified, as they control G0. In the fission yeast Schizosaccharomyces pombe, haploid cells are completely arrested under nitrogen source starvation with high viability. We examined the global transcriptome of G0 cells and cells on the course to resume vegetative growth. Approximately 20% of the transcripts of approximately 5000 genes increased or decreased more than fourfold in the two-step transitions that occur prior to replication. Of the top 30 abundant transcripts in G0, 23 were replaced by ribosome- and translation-related transcripts in the dividing vegetative state. Eight identified clusters with distinct alteration patterns of approximately 2700 transcripts were annotated by Gene Ontology. Disruption of 53 genes indicated that nine of them were necessary to support the proper G0 state. These nine genes included two C2H2 zinc finger transcription factors, a cyclin-like protein implicated in phosphorylation of RNA polymerase II, two putative autophagy regulators, a G-protein activating factor, and two CBS domain proteins, possibly involved in AMP-activated kinase.
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PMID:Two-step, extensive alterations in the transcriptome from G0 arrest to cell division in Schizosaccharomyces pombe. 1753 57

Brd4 is a bromodomain protein that binds to acetylated chromatin. It regulates cell growth, although the underlying mechanism has remained elusive. Brd4 has also been shown to control transcription of viral genes, whereas its role in transcription of cellular genes has not been fully elucidated. Here we addressed the role of Brd4 in cell growth and transcription using a small hairpin (sh) RNA approach. The Brd4 shRNA vector stably knocked down Brd4 protein expression by approximately 90% in NIH3T3 cells and mouse embryonic fibroblasts. Brd4 knockdown cells were growth impaired and grew more slowly than control cells. When synchronized by serum starvation and released, Brd4 knockdown cells were arrested at G(1), whereas control cells progressed to S phase. In microarray analysis, although numerous genes were up-regulated during G(1) in control cells, many of these G(1) genes were not up-regulated in Brd4 knockdown cells. Reintroduction of Brd4 rescued expression of these G(1) genes in Brd4 knockdown cells, allowing cells to progress toward S phase. Chromatin immunoprecipitation analysis showed that Brd4 was recruited to the promoters of these G(1) genes during G(0)-G(1) progression. Furthermore, Brd4 recruitment coincided with increased binding of Cdk9, a component of P-TEFb and RNA polymerase II to these genes. Brd4 recruitment was low to absent at genes not affected by Brd4 shRNA. The results indicate that Brd4 stimulates G(1) gene expression by binding to multiple G(1) gene promoters in a cell cycle-dependent manner.
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PMID:The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase. 1822 96


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