Synonymous and Nonsynonymous Substitutions in Dictyostelium discoideum Ammonium Transporter Are Necessary for Functional Complementation in Saccharomyces cerevisiae.

Ammonium transporters are present in all three domains of life. They have undergone extensive horizontal gene transfer (HGT), gene duplication, and functional diversification and therefore offer an excellent paradigm to study protein evolution. We attempted to complement a ΔΔΔ strain of Saccharomyces cerevisiae (triple-deletion strain), which otherwise cannot grow on ammonium as a sole nitrogen source at concentrations of <3 mM, with of Dictyostelium discoideum, an orthologue of S.

Trehalose biosynthetic pathway regulates filamentation response in Saccharomyces cerevisiae.

Background: Diploid cells of Saccharomyces cerevisiae undergo either pseudohyphal differentiation or sporulation in response to depletion of carbon and nitrogen sources. Distinct signaling pathways regulate filamentation and sporulation in response to nutrient limitation. How these pathways are coordinated for implementing distinct cell fate decisions in response to similar nutritional cues is an enigma.

Fermentative metabolism impedes p53-dependent apoptosis in a Crabtree-positive but not in Crabtree-negative yeast.

Tumour cells distinguish from normal cells by fermenting glucose to lactate in presence of sufficient oxygen and functional mitochondria (Warburg effect). Crabtree effect was invoked to explain the biochemical basis of Warburg effect by suggesting that excess glucose suppresses mitochondrial respiration. It is known that the Warburg effect and Crabtree effect are displayed by , during growth on abundant glucose.

KRH1 and KRH2 are functionally non-redundant in signaling for pseudohyphal differentiation in Saccharomyces cerevisiae.

Diploid cells of Saccharomyces cerevisiae undergo pseudohyphal differentiation in response to nutrient depletion. Although this dimorphic transition occurs due to signals originating from carbon and nitrogen limitation, how these signals are coordinated and integrated is not understood. Results of this study indicate that the pseudohyphal defect of the mep2∆ mutant is overcome upon disruption of KRH2/GPB1 but not KRH1/GPB2.

Multiple Conformations of Gal3 Protein Drive the Galactose-Induced Allosteric Activation of the GAL Genetic Switch of Saccharomyces cerevisiae.

Gal3p is an allosteric monomeric protein that activates the GAL genetic switch of Saccharomyces cerevisiae in response to galactose. Expression of constitutive mutant of Gal3p or overexpression of wild-type Gal3p activates the GAL switch in the absence of galactose. These data suggest that Gal3p exists as an ensemble of active and inactive conformations.

The binary response of the GAL/MEL genetic switch of Saccharomyces cerevisiae is critically dependent on Gal80p-Gal4p interaction.

Studies on the Saccharomyces cerevisiae GAL/MEL genetic switch have revealed that its bistability is dependent on ultrasensitivity that can be altered or abolished by disabling different combinations of nested feedback loops. In contrast, we have previously demonstrated that weakening of the interaction between Gal80p and Gal4p alone is sufficient to abolish the ultrasensitivity (Das Adhikari et al. 2014).

Perturbation of the interaction between Gal4p and Gal80p of the Saccharomyces cerevisiae GAL switch results in altered responses to galactose and glucose.

In S. cerevisiae, following the Whole Genome Duplication (WGD), GAL1-encoded galactokinase retained its signal transduction function but lost basal expression. On the other hand, its paralogue GAL3, lost kinase activity but retained its signalling function and basal expression, thus making it indispensable for the rapid induction of the S.

Stochastic galactokinase expression underlies GAL gene induction in a GAL3 mutant of Saccharomyces cerevisiae.

GAL1 and GAL3 are paralogous signal transducers that functionally inactivate Gal80p to activate the Gal4p-dependent transcriptional activation of GAL genes in Saccharomyces cerevisiae in response to galactose. Unlike a wild-type strain, the gal3∆ strain shows delayed growth kinetics as a result of the signaling function of GAL1. The mechanism ensuring that GAL1 is eventually expressed to turn on the GAL switch in the gal3∆ strain remains a paradox.

Can metabolic plasticity be a cause for cancer? Warburg-Waddington legacy revisited.

Unlabelled: Fermentation of glucose to lactate in the presence of sufficient oxygen, known as aerobic glycolysis or Warburg effect, is a universal phenotype of cancer cells. Understanding its origin and role in cellular immortalization and transformation has attracted considerable attention in the recent past. Intriguingly, while we now know that Warburg effect is essential for tumor growth and development, it is thought to arise because of genetic and/or epigenetic changes.

Systems biology of GAL regulon in Saccharomyces cerevisiae.

Evolutionary success of an organism depends on its ability to express or adapt to constantly changing environmental conditions. Saccharomyces cerevisiae has evolved an elaborate genetic circuit to regulate the expression of galactose-metabolizing enzymes in the presence of galactose but in the absence of glucose. The circuit possesses molecular mechanisms such as multiple binding sites, cooperativity, autoregulation, nucleocytoplasmic shuttling, and substrate sensing mechanism.

Epigenetics of the yeast galactose genetic switch.

The transcriptional activation of enzymes involved in galactose utilization (GAL genes) in Saccharomyces cerevisiae is regulated by a complex interplay between three regulatory proteins encoded by GAL4 (transcriptional activator), GAL3 (signal transducer) and GAL80 (repressor). The relative concentrations of the signal transducer and the repressor are maintained by autoregulation. Cells disabled for autoregulation exhibit phenotypes distinctly different from that of the wild type cells, enabling us to explore the biological significance of autoregulation.

Pseudohyphal differentiation defect due to mutations in GPCR and ammonium signaling is suppressed by low glucose concentration: a possible integrated role for carbon and nitrogen limitation.

In response to carbon and/or nitrogen limitation, diploid cells of Saccharomyces cerevisiae either sporulate or develop pseudohyphae. Although the signal transduction pathways leading to these developmental changes have been extensively studied, how nutritional signals are integrated is not clearly understood. Results of this study indicate that reducing glucose concentration from 2% (SLAD) to 0.

Biological significance of autoregulation through steady state analysis of genetic networks.

Autoregulation of regulatory proteins is a recurring theme in genetic networks. Autoregulation is an important component of a genetic regulatory network besides protein-protein and protein-DNA interactions, stoichiometry, multiple binding sites and cooperativity. Although the biological significance of autoregulation has been studied before, its significance in presence of other mechanisms is not clearly enumerated.

Replacement of a conserved tyrosine by tryptophan in Gal3p of Saccharomyces cerevisiae reduces constitutive activity: implications for signal transduction in the GAL regulon.

The ability of Saccharomyces cerevisiae to utilize galactose is regulated by the nucleo-cytoplasmic shuttling of a transcriptional repressor, the Gal80 protein. Gal80 interacts with the transcriptional activator Gal4 in the nucleus and inhibits its function, preventing induction of the GAL genes. In response to galactose, the relative amounts of Gal80 in the cytoplasm and the nucleus are modulated by the action of a signal transducer, Gal3.

Stochastic variation in the concentration of a repressor activates GAL genetic switch: implications in evolution of regulatory network.

In Saccharomyces cerevisiae, a recessive mutation in the signal transducer encoded by GAL3 leads to a significant lag in the induction of GAL genes, referred to as long term adaptation phenotype (LTA). Further, gal3 mutation in combination with other genetic defects leads to the non-inducibility of GAL genes. It was shown that the expression of GAL1 encoded galactokinase, a redundant GAL3 like signal transducer, eventually substitutes for the lack of GAL3 signal transduction function.

Disruption of MRG19 results in altered nitrogen metabolic status and defective pseudohyphal development in Saccharomyces cerevisiae.

It was previously shown that MRG19 downregulates carbon metabolism in Saccharomyces cerevisiae upon glucose exhaustion, and that the gene is glucose repressed. Here, it is shown that glucose repression of MRG19 is overcome upon nitrogen withdrawal, suggesting that MRG19 is a regulator of carbon and nitrogen metabolism. beta-Galactosidase activity fostered by the promoter of GDH1/3, which encode anabolic enzymes of nitrogen metabolism, was altered in an MRG19 disruptant.

Quantitative analysis of GAL genetic switch of Saccharomyces cerevisiae reveals that nucleocytoplasmic shuttling of Gal80p results in a highly sensitive response to galactose.

The nucleocytoplasmic shuttling of the repressor Gal80p is known to play a pivotal role in the signal transduction process of GAL genetic switch of Saccharomyces cerevisiae (Peng, G., and Hopper, J. E.

Expression of GAL genes in a mutant strain of Saccharomyces cerevisiae lacking GAL80: quantitative model and experimental verification.

The regulatory network of GAL genes is a model system for the production of foreign proteins. A mathematical model based on steady state was developed for the expression of GAL (galactosidase) genes in a mutant strain of Saccharomyces cerevisiae lacking GAL80. The transcriptional and translational responses of the GAL switch were predicted at various steady-state glucose concentrations.

Galactose-1-phosphate is a regulator of inositol monophosphatase: a fact or a fiction?

Classic galactosemia is due to the deficiency of galactose-1-phosphate uridyl transferase and is transmitted as an autosomal recessive disorder. Patients suffering from classic galactosemia display acute symptoms such as poor growth, feeding difficulties, jaundice, hepatomegaly etc., which disappear when the individual is on galactose free diet.

Molecular characterization of MRG19 of Saccharomyces cerevisiae. Implication in the regulation of galactose and nonfermentable carbon source utilization.

We have reported previously that multiple copies of MRG19 suppress GAL genes in a wild-type but not in a gal80 strain of Saccharomyces cerevisiae. In this report we show that disruption of MRG19 leads to a decrease in GAL induction when S. cerevisiae is induced with 0.