scholarly journals Genetic Analysis of the Shared Role of CLN3 and BCK2 at the G1-S Transition in Saccharomyces cerevisiae

Genetics ◽  
1999 ◽  
Vol 153 (3) ◽  
pp. 1131-1143
Author(s):  
Herman Wijnen ◽  
Bruce Futcher
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Analysis ◽  
Target Genes ◽  
S Phase ◽  
Negative Regulator ◽  
Growth Defect ◽  
Uncharacterized Protein ◽  
Number Of Genes ◽  
Transcription Complexes

Abstract The transcription complexes SBF and MBF mediate the G1-S transition in the cell cycle of Saccharomyces cerevisiae. In late G1, SBF and MBF induce a burst of transcription in a number of genes, including G1- and S-phase cyclins. Activation of SBF and MBF depends on the G1 cyclin Cln3 and a largely uncharacterized protein called Bck2. We show here that the induction of SBF/MBF target genes by Bck2 depends partly, but not wholly, on SBF and MBF. Unlike Cln3, Bck2 is capable of inducing its transcriptional targets in the absence of functional Cdc28. Our results revealed promoter-specific mechanisms of regulation by Cln3, Bck2, SBF, and MBF. We isolated high-copy suppressors of the cln3 bck2 growth defect; all of these had the ability to increase CLN2 expression. One of these suppressors was the negative regulator of meiosis RME1. Rme1 induces CLN2, and we show that it has a haploid-specific role in regulating cell size and pheromone sensitivity. Genetic analysis of the cln3 bck2 defect showed that CLN1, CLN2, and other SBF/MBF target genes have an essential role in addition to the degradation of Sic1.

Global regulation of mitochondrial biogenesis in Saccharomyces cerevisiae: ABF1 and CPF1 play opposite roles in regulating expression of the QCR8 gene, which encodes subunit VIII of the mitochondrial ubiquinol-cytochrome c oxidoreductase

1992 ◽  
Vol 12 (6) ◽  
pp. 2872-2883
Author(s):  
J H de Winde ◽  
L A Grivell
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cytochrome C ◽  
Mitochondrial Biogenesis ◽  
Binding Sites ◽  
Promoter Region ◽  
S Phase ◽  
Negative Regulator ◽  
Global Regulation ◽  
Two Factors ◽  
Efficient Induction

The multifunctional DNA-binding proteins ABF1 and CPF1 bind in a mutually exclusive manner to the promoter region of the QCR8 gene, which encodes 11-kDa subunit VIII of the Saccharomyces cerevisiae mitochondrial ubiquinol-cytochrome c oxidoreductase (QCR). We investigated the roles that the two factors play in transcriptional regulation of this gene. To this end, the overlapping binding sites for ABF1 and CPF1 were mutated and placed in the chromosomal context of the QCR8 promoter. The effects on transcription of the QCR8 gene were analyzed both under steady-state conditions and during nutritional shifts. We found that ABF1 is required for repressed and derepressed transcription levels and for efficient induction of transcription upon escape from catabolite repression, independently of DNA replication. CPF1 acts as a negative regulator, modulating the overall induction response. Alleviation of repression through CPF1 requires passage through the S phase. Implications of these findings for the roles played by ABF1 and CPF1 in global regulation of mitochondrial biogenesis are discussed.

scholarly journals Role of Cdc42-Cla4 Interaction in the Pheromone Response of Saccharomyces cerevisiae

2006 ◽  
Vol 6 (2) ◽  
pp. 317-327 ◽  
Author(s):  
Melanie Heinrich ◽  
Tim Köhler ◽  
Hans-Ulrich Mösch
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Map Kinase ◽  
Cell Cycle Arrest ◽  
Map Kinases ◽  
Negative Regulator ◽  
Cycle Arrest ◽  
Mitogen Activated Protein ◽  
Novel Alleles

ABSTRACT In Saccharomyces cerevisiae, the highly conserved Rho-type GTPase Cdc42 is essential for cell division and controls cellular development during mating and invasive growth. The role of Cdc42 in mating has been controversial, but a number of previous studies suggest that the GTPase controls the mitogen-activated protein (MAP) kinase cascade by activating the p21-activated protein kinase (PAK) Ste20. To further explore the role of Cdc42 in pheromone-stimulated signaling, we isolated novel alleles of CDC42 that confer resistance to pheromone. We find that in CDC42(V36A) and CDC42(V36A, I182T) mutant strains, the inability to undergo pheromone-induced cell cycle arrest correlates with reduced phosphorylation of the mating MAP kinases Fus3 and Kss1 and with a decrease in mating efficiency. Furthermore, Cdc42(V36A) and Cdc42(V36A, I182T) proteins show reduced interaction with the PAK Cla4 but not with Ste20. We also show that deletion of CLA4 in a CDC42(V36A, I182T) mutant strain suppresses pheromone resistance and that overexpression of CLA4 interferes with pheromone-induced cell cycle arrest and MAP kinase phosphorylation in CDC42 wild-type strains. Our data indicate that Cla4 has the potential to act as a negative regulator of the mating pathway and that this function of the PAK might be under control of Cdc42. In conclusion, our study suggests that control of pheromone signaling by Cdc42 not only depends on Ste20 but also involves interaction of the GTPase with Cla4.

scholarly journals A Genomewide Screen for Tolerance to Cationic Drugs Reveals Genes Important for Potassium Homeostasis in Saccharomyces cerevisiae

2011 ◽  
Vol 10 (9) ◽  
pp. 1241-1250 ◽  
Author(s):  
Lina Barreto ◽  
David Canadell ◽  
Silvia Petrezsélyová ◽  
Clara Navarrete ◽  
Lydie Marešová ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Potassium Concentration ◽  
Growth Defect ◽  
Electrochemical Gradient ◽  
Biochemical Tests ◽  
Content Type ◽  
Potassium Homeostasis ◽  
Moderate Growth ◽  
Number Of Genes ◽  
Mutant Strains

ABSTRACTPotassium homeostasis is crucial for living cells. In the yeastSaccharomyces cerevisiae, the uptake of potassium is driven by the electrochemical gradient generated by the Pma1 H+-ATPase, and this process represents a major consumer of the gradient. We considered that any mutation resulting in an alteration of the electrochemical gradient could give rise to anomalous sensitivity to any cationic drug independently of its toxicity mechanism. Here, we describe a genomewide screen for mutants that present altered tolerance to hygromycin B, spermine, and tetramethylammonium. Two hundred twenty-six mutant strains displayed altered tolerance to all three drugs (202 hypersensitive and 24 hypertolerant), and more than 50% presented a strong or moderate growth defect at a limiting potassium concentration (1 mM). Functional groups such as protein kinases and phosphatases, intracellular trafficking, transcription, or cell cycle and DNA processing were enriched. Essentially, our screen has identified a substantial number of genes that were not previously described to play a direct or indirect role in potassium homeostasis. A subset of 27 representative mutants were selected and subjected to diverse biochemical tests that, in some cases, allowed us to postulate the basis for the observed phenotypes.

scholarly journals Role of Heat Shock Transcription Factor in Saccharomyces cerevisiae Oxidative Stress Response

2007 ◽  
Vol 6 (8) ◽  
pp. 1373-1379 ◽  
Author(s):  
Ayako Yamamoto ◽  
Junko Ueda ◽  
Noritaka Yamamoto ◽  
Naoya Hashikawa ◽  
Hiroshi Sakurai
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Stress Response ◽  
Heat Shock ◽  
Superoxide Anion ◽  
Target Genes ◽  
Oxidative Stress Response ◽  
Heat Shock Transcription Factor ◽  
Negative Regulator

ABSTRACT The heat shock transcription factor Hsf1 of the yeast Saccharomyces cerevisiae regulates the transcription of a set of genes that contain heat shock elements (HSEs) in their promoters and function in diverse cellular processes, including protein folding. Here, we show that Hsf1 activates the transcription of various target genes when cells are treated with oxidizing reagents, including the superoxide anion generators menadione and KO2 and the thiol oxidants diamide and 1-chloro-2,4-dinitrobenzene (CDNB). Similar to heat shock, the oxidizing reagents are potent inducers of both efficient HSE binding and extensive phosphorylation of Hsf1. The inducible phosphorylation of Hsf1 is regulated by the intramolecular domain-domain interactions and affects HSE structure-specific transcription. Unlike the heat shock, diamide, or CDNB response, menadione or KO2 activation of Hsf1 is inhibited by cyclic-AMP-dependent protein kinase (PKA) activity, which negatively regulates the activator functions of other transcriptional regulators implicated in the oxidative stress response. These results demonstrate that Hsf1 is a member of the oxidative stress-responsive activators and that PKA is a general negative regulator in the superoxide anion response.

scholarly journals Cell Cycle Control of Cdc7p Kinase Activity through Regulation of Dbf4p Stability

1999 ◽  
Vol 19 (7) ◽  
pp. 4888-4896 ◽  
Author(s):  
Guy Oshiro ◽  
Julia C. Owens ◽  
Yiqun Shellman ◽  
Robert A. Sclafani ◽  
Joachim J. Li
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Dna Replication ◽  
Kinase Activity ◽  
Cell Cycle Control ◽  
S Phase ◽  
Regulatory Subunit ◽  
Anaphase Promoting Complex ◽  
Initiation Of Dna Replication

ABSTRACT In Saccharomyces cerevisiae, the heteromeric kinase complex Cdc7p-Dbf4p plays a pivotal role at replication origins in triggering the initiation of DNA replication during the S phase. We have assayed the kinase activity of endogenous levels of Cdc7p kinase by using a likely physiological target, Mcm2p, as a substrate. Using this assay, we have confirmed that Cdc7p kinase activity fluctuates during the cell cycle; it is low in the G1 phase, rises as cells enter the S phase, and remains high until cells complete mitosis. These changes in kinase activity cannot be accounted for by changes in the levels of the catalytic subunit Cdc7p, as these levels are constant during the cell cycle. However, the fluctuations in kinase activity do correlate with levels of the regulatory subunit Dbf4p. The regulation of Dbf4p levels can be attributed in part to increased degradation of the protein in G1 cells. This G1-phase instability is cdc16 dependent, suggesting a role of the anaphase-promoting complex in the turnover of Dbf4p. Overexpression of Dbf4p in the G1 phase can partially overcome this elevated turnover and lead to an increase in Cdc7p kinase activity. Thus, the regulation of Dbf4p levels through the control of Dbf4p degradation has an important role in the regulation of Cdc7p kinase activity during the cell cycle.

scholarly journals Mitotic Cyclins Regulate Telomeric Recombination in Telomerase-Deficient Yeast Cells

2003 ◽  
Vol 23 (24) ◽  
pp. 9162-9177 ◽  
Author(s):  
Nathalie Grandin ◽  
Michel Charbonneau
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Interaction ◽  
Mitotic Cell ◽  
Nuclease Activity ◽  
Yeast Cells ◽  
Growth Defect ◽  
Mitotic Cell Cycle ◽  
Functional Interaction ◽  
Synthetic Growth

ABSTRACT Telomerase-deficient mutants of Saccharomyces cerevisiae can survive death by senescence by using one of two homologous recombination pathways. The Rad51 pathway amplifies the subtelomeric Y′ sequences, while the Rad50 pathway amplifies the telomeric TG1-3 repeats. Here we show that telomerase-negative cells require Clb2 (the major B-type cyclin in this organism), in association with Cdc28 (Cdk1), to generate postsenescence survivors at a normal rate. The Rad50 pathway was more sensitive to the absence of Clb2 than the Rad51 pathway. We also report that telomerase RAD50 RAD51 triple mutants still generated postsenescence survivors. This novel Rad50- and Rad51-independent pathway of telomeric recombination also appeared to be controlled by Clb2. In telomerase-positive cells, a synthetic growth defect between mutations in CLB2 and RAD50 or in its partners in the conserved MRX complex, MRE11 and XRS2, was observed. This genetic interaction was independent of Mre11 nuclease activity but was dependent on a DNA repair function. The present data reveal an unexpected role of Cdc28/Clb2 in telomeric recombination during telomerase-independent maintenance of telomeres. They also uncover a functional interaction between Cdc28/Clb2 and MRX during the control of the mitotic cell cycle.

scholarly journals A novel role of MNT as a negative regulator of REL and the NF-κB pathway

Oncogenesis ◽  
2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Judit Liaño-Pons ◽  
M. Carmen Lafita-Navarro ◽  
Lorena García-Gaipo ◽  
Carlota Colomer ◽  
Javier Rodríguez ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Transcriptional Regulator ◽  
Negative Regulator ◽  
Biological Processes ◽  
Helix Loop Helix ◽  
Bona Fide ◽  
E Boxes ◽  
Independent Protein

AbstractMNT, a transcription factor of the MXD family, is an important modulator of the oncoprotein MYC. Both MNT and MYC are basic-helix–loop–helix proteins that heterodimerize with MAX in a mutually exclusive manner, and bind to E-boxes within regulatory regions of their target genes. While MYC generally activates transcription, MNT represses it. However, the molecular interactions involving MNT as a transcriptional regulator beyond the binding to MAX remain unexplored. Here we demonstrate a novel MAX-independent protein interaction between MNT and REL, the oncogenic member of the NF-κB family. REL participates in important biological processes and it is altered in a variety of tumors. REL is a transcription factor that remains inactive in the cytoplasm in an inhibitory complex with IκB and translocates to the nucleus when the NF-κB pathway is activated. In the present manuscript, we show that MNT knockdown triggers REL translocation into the nucleus and thus the activation of the NF-κB pathway. Meanwhile, MNT overexpression results in the repression of IκBα, a bona fide REL target. Both MNT and REL bind to the IκBα gene on the first exon, suggesting its regulation as an MNT–REL complex. Altogether our data indicate that MNT acts as a repressor of the NF-κB pathway by two mechanisms: (1) retention of REL in the cytoplasm by MNT interaction, and (2) MNT-driven repression of REL-target genes through an MNT–REL complex. These results widen our knowledge about MNT biological roles and reveal a novel connection between the MYC/MXD and NF-κB pathways, two of the most prominent pathways in cancer.

scholarly journals A STUDY OF THE ROLE OF MICRORNA IN PITUITARY ADENOMA

2018 ◽  
Vol 5 (2) ◽  
pp. 8-15
Author(s):  
I. F. Gareev ◽  
O. A. Beylerli
Keyword(s):  
Pituitary Adenoma ◽  
Target Genes ◽  
Decisive Role ◽  
Cellular Processes ◽  
New Class ◽  
Number Of Genes ◽  
Non Coding Rnas ◽  
New Biomarkers ◽  
New Evidence

MicroRNAs are a new class of small non-coding RNAs, a length of 18–22 nucleotides that play a decisive role as posttranscriptional regulators of gene expression. Due to the large number of genes, regulated microRNAs, microRNAs are involved in many cellular processes. The study of the impairment of the expression of the target genes of microRNA, often associated with changes in important biological characteristics, provides a significant understanding of the role of microRNAs in oncogenesis. New evidence suggests that aberrant microRNA expression or dysregulation of endogenous microRNAs affects the onset and development of tumors, including adenomas of the pituitary gland. In this review, the significance of some microRNAs in the pathology of the pituitary adenoma will be assessed, as well as data on the study of microRNAs as therapeutic targets and new biomarkers.

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