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Soumya Moonjely, Nemat O Keyhani, Michael J Bidochka
The hyd1/hyd2 hydrophobins are important constituents of the conidial cell wall of the insect pathogenic fungus Beauveria bassiana. This fungus can also form intimate associations with several plant species. Here, we show that inactivation of two Class I hydrophobin genes, hyd1 or hyd2, significantly decreases the interaction of B. bassiana with bean roots. Curiously, the ∆hyd1/∆hyd2 double mutant was less impaired in root association than Δhyd1 or Δhyd2. Loss of hyd genes affected growth rate, conidiation ability and oosporein production...
March 8, 2018: Microbiology
Zheng Kuang, Hongkai Ji, Jef D Boeke
Quiescent cells exploit an array of transcription factors to activate stress response machinery and maintain survival under nutrient-limited conditions. Our recent findings reveal that these transcription factors also play an important role in the exit of quiescence and regrowth. By studying Saccharomyces cerevisiae under a continuous, nutrient-limited condition, we found that Msn2 and Msn4 function as master regulators of glycolytic genes in the quiescent-like phase. They control the timing of transition from quiescence to growth by regulating the accumulation rate of acetyl-CoA, a key metabolite that is downstream of glycolysis and drives growth...
February 17, 2018: Current Genetics
Audrey P Gasch, Feiqiao Brian Yu, James Hose, Leah E Escalante, Mike Place, Rhonda Bacher, Jad Kanbar, Doina Ciobanu, Laura Sandor, Igor V Grigoriev, Christina Kendziorski, Stephen R Quake, Megan N McClean
From bacteria to humans, individual cells within isogenic populations can show significant variation in stress tolerance, but the nature of this heterogeneity is not clear. To investigate this, we used single-cell RNA sequencing to quantify transcript heterogeneity in single Saccharomyces cerevisiae cells treated with and without salt stress to explore population variation and identify cellular covariates that influence the stress-responsive transcriptome. Leveraging the extensive knowledge of yeast transcriptional regulation, we uncovered significant regulatory variation in individual yeast cells, both before and after stress...
December 2017: PLoS Biology
Yutaro Yamaguchi, Yuka Katsuki, Seiya Tanaka, Ryotaro Kawaguchi, Hiroto Denda, Takuma Ikeda, Kouichi Funato, Motohiro Tani
Complex sphingolipids play critical roles in various cellular events in the yeast Saccharomyces cerevisiae. To identify genes that are related to the growth defect caused by disruption of complex sphingolipid biosynthesis, we screened for suppressor mutations and multicopy suppressor genes that confer resistance against repression of AUR1 encoding inositol phosphorylceramide synthase. From the results of this screening, we found that the activation of high-osmolarity glycerol (HOG) pathway is involved in suppression of growth defect caused by impaired biosynthesis of complex sphingolipids...
February 2018: Molecular Microbiology
Pengsong Li, Xiaofen Fu, Lei Zhang, Zhiyu Zhang, Jihong Li, Shizhong Li
Background: High temperature inhibits cell growth and ethanol fermentation of Saccharomyces cerevisiae . As a complex phenotype, thermotolerance usually involves synergistic actions of many genes, thereby being difficult to engineer. The overexpression of either endogenous or exogenous stress-related transcription factor genes in yeasts was found to be able to improve relevant stress tolerance of the hosts. Results: To increase ethanol yield of high-temperature fermentation, we constructed a series of strains of S...
2017: Biotechnology for Biofuels
Ariadne Vlahakis, Nerea Lopez Muniozguren, Ted Powers
Macroautophagy/autophagy is a starvation and stress-induced catabolic process critical for cellular homeostasis and adaptation. Several Atg proteins are involved in the formation of the autophagosome and subsequent degradation of cytoplasmic components, a process termed autophagy flux. Additionally, the expression of several Atg proteins, in particular Atg8, is modulated transcriptionally, yet the regulatory mechanisms involved remain poorly understood. Here we demonstrate that the AGC kinase Ypk1, target of the rapamycin-insensitive TORC2 signaling pathway, controls ATG8 expression by repressing the heterodimeric Zinc-finger transcription factors Msn2 and Msn4...
2017: Autophagy
Longyan Tian, Jun Yu, Yonglin Wang, Chengming Tian
Verticillium dahliae is a notorious pathogen that causes vascular wilt disease in numerous plant species worldwide. The fungus produces melanized microsclerotia, which helps it survive adverse environmental conditions that it may encounter within its hosts and in the soil. Previously, we determined that the high osmolarity glycerol (HOG) pathway is involved in the environmental stress response of V. dahliae. In this study, we investigated the function of VdMsn2, a homologue of the yeast C2H2 transcription factor Msn2, which is predicted to function as a downstream player in the HOG pathway...
December 2017: Fungal Biology
Liangtao Li, Diane M Ward
All eukaryotes require the transition metal, iron, a redox active element that is an essential cofactor in many metabolic pathways, as well as an oxygen carrier. Iron can also react to generate oxygen radicals such as hydroxyl radicals and superoxide anions, which are highly toxic to cells. Therefore, organisms have developed intricate mechanisms to acquire iron as well as to protect themselves from the toxic effects of excess iron. In fungi and plants, iron is stored in the vacuole as a protective mechanism against iron toxicity...
October 17, 2017: Current Genetics
Zheng Kuang, Sudarshan Pinglay, Hongkai Ji, Jef D Boeke
Nutrient availability and stresses impact a cell's decision to enter a growth state or a quiescent state. Acetyl-CoA stimulates cell growth under nutrient-limiting conditions, but how cells generate acetyl-CoA under starvation stress is less understood. Here, we show that general stress response factors, Msn2 and Msn4, function as master transcriptional regulators of yeast glycolysis via directly binding and activating genes encoding glycolytic enzymes. Yeast cells lacking Msn2 and Msn4 exhibit prevalent repression of glycolytic genes and a significant delay of acetyl-CoA accumulation and reentry into growth from quiescence...
September 26, 2017: ELife
Praveen Kumar Rajvanshi, Madhuri Arya, Ram Rajasekharan
The transcription factors Msn2 and Msn4 (multicopy suppressor of SNF1 mutation proteins 2 and 4) bind the stress-response element in gene promoters in the yeast Saccharomyces cerevisiae However, the roles of Msn2/4 in primary metabolic pathways such as fatty acid β-oxidation are unclear. Here, in silico analysis revealed that the promoters of most genes involved in the biogenesis, function, and regulation of the peroxisome contain Msn2/4-binding sites. We also found that transcript levels of MSN2/MSN4 are increased in glucose-depletion conditions and that during growth in nonpreferred carbon sources, Msn2 is constantly localized to the nucleus in wild-type cells...
November 10, 2017: Journal of Biological Chemistry
Liangtao Li, Jerry Kaplan, Diane M Ward
The budding yeast Saccharomyces cerevisiae stores iron in the vacuole, which is a major resistance mechanism against iron toxicity. One key protein involved in vacuolar iron storage is the iron importer Ccc1, which facilitates iron entry into the vacuole. Transcription of the CCC1 gene is largely regulated by the binding of iron-sulfur clusters to the activator domain of the transcriptional activator Yap5. Additional evidence, however, suggests that Yap5-independent transcriptional activation of CCC1 also contributes to iron resistance...
September 15, 2017: Journal of Biological Chemistry
Yuan Wu, Yanna Ren, Xiangshan Zhou, Menghao Cai, Yuanxing Zhang
Fungi possess sophisticated regulatory systems to respond to a vast array of environmental signals. Among these responsive networks, some genes play critical roles in the regulation of various cellular processes. Here, we identified a putative transcriptional factor Agseb1 in Aspergillus glaucus, a marine-derived filamentous fungus. Agseb1 encodes a protein with two C2 H2 zinc fingers at the C-terminus, similar to the placement of these motifs in msn2/4 of Saccharomyces cerevisia, where they are positioned to allow binding to the CCCCT-box of stress-specific genes...
July 26, 2017: Journal of Basic Microbiology
Raúl García, Enrique Bravo, Sonia Diez-Muñiz, Cesar Nombela, Jose M Rodríguez-Peña, Javier Arroyo
Fungal cells trigger adaptive mechanisms to survive in situations that compromise cell wall integrity. We show here that the global transcriptional response elicited by inhibition of the synthesis of β-1,3-glucan by caspofungin, encompasses a set of genes that are dependent on Slt2, the MAPK of the Cell Wall Integrity (CWI) pathway, and a broad group of genes regulated independently of Slt2. Genes negatively regulated by the cyclic AMP/Protein Kinase A (PKA) signaling pathway were overrepresented in the latter group...
July 18, 2017: Scientific Reports
Ya-Lan Chang, Shun-Fu Tseng, Yu-Ching Huang, Zih-Jie Shen, Pang-Hung Hsu, Meng-Hsun Hsieh, Chia-Wei Yang, Silvia Tognetti, Berta Canal, Laia Subirana, Chien-Wei Wang, Hsiao-Tan Chen, Chi-Ying Lin, Francesc Posas, Shu-Chun Teng
Upon environmental changes, proliferating cells delay cell cycle to prevent further damage accumulation. Yeast Cip1 is a Cdk1 and Cln2-associated protein. However, the function and regulation of Cip1 are still poorly understood. Here we report that Cip1 expression is co-regulated by the cell-cycle-mediated factor Mcm1 and the stress-mediated factors Msn2/4. Overexpression of Cip1 arrests cell cycle through inhibition of Cdk1-G1 cyclin complexes at G1 stage and the stress-activated protein kinase-dependent Cip1 T65, T69, and T73 phosphorylation may strengthen the Cip1and Cdk1-G1 cyclin interaction...
July 4, 2017: Nature Communications
Sophie A Comyn, Stéphane Flibotte, Thibault Mayor
Proteostasis promotes viability at both the cellular and organism levels by maintaining a functional proteome. This requires an intricate protein quality control (PQC) network that mediates protein folding by molecular chaperones and removes terminally misfolded proteins via the ubiquitin proteasome system and autophagy. How changes within the PQC network can perturb proteostasis and shift the balance between protein folding and proteolysis remain poorly understood. However, given that proteostasis is altered in a number of conditions such as cancer and ageing, it is critical that we identify the factors that mediate PQC and understand the interplay between members of the proteostatic network...
June 23, 2017: Scientific Reports
Yanfei Jiang, Zohreh AkhavanAghdam, Lev S Tsimring, Nan Hao
Information about environmental stimuli often can be encoded by the dynamics of signaling molecules or transcription factors. In the yeast Saccharomyces cerevisiae, different types of stresses induce distinct nuclear translocation dynamics of the general stress-responsive transcription factor Msn2, but the underlying mechanisms remain unclear. Using deterministic and stochastic modeling, we reproduced in silico the different dynamic responses of Msn2 to glucose limitation and osmotic stress observed in vivo and found that a positive feedback loop on protein kinase A mediated by the AMP-activated protein kinase Snf1 is coupled with a negative feedback loop to generate the characteristic pulsatile dynamics of Msn2...
July 28, 2017: Journal of Biological Chemistry
Ana Fátima Amorim, Dora Pinto, Laurent Kuras, Lisete Fernandes
Saccharomyces cerevisiae GimC (mammalian Prefoldin) is a hexameric (Gim1-6) cytoplasmic complex involved in the folding pathway of actin/tubulin. In contrast to a shared role in GimC complex, we show that absence of individual Gim proteins results in distinct stress responses. No concomitant alteration in F-actin integrity was observed. Transcription of stress responsive genes is altered in gim2Δ, gim3Δ and gim6Δ mutants: TRX2 gene is induced in these mutants but with a profile diverging from type cells, whereas CTT1 and HSP26 fail to be induced...
July 2017: Biochimica et Biophysica Acta
Stefano Di Biase, Hong Seok Shim, Kyung Hwa Kim, Manlio Vinciguerra, Francesca Rappa, Min Wei, Sebastian Brandhorst, Francesco Cappello, Hamed Mirzaei, Changhan Lee, Valter D Longo
Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone...
March 2017: PLoS Biology
Kristofer Bodvard, Ken Peeters, Friederike Roger, Natalie Romanov, Aeid Igbaria, Niek Welkenhuysen, Gaël Palais, Wolfgang Reiter, Michel B Toledano, Mikael Käll, Mikael Molin
Yeast lacks dedicated photoreceptors; however, blue light still causes pronounced oscillations of the transcription factor Msn2 into and out of the nucleus. Here we show that this poorly understood phenomenon is initiated by a peroxisomal oxidase, which converts light into a hydrogen peroxide (H2O2) signal that is sensed by the peroxiredoxin Tsa1 and transduced to thioredoxin, to counteract PKA-dependent Msn2 phosphorylation. Upon H2O2, the nuclear retention of PKA catalytic subunits, which contributes to delayed Msn2 nuclear concentration, is antagonized in a Tsa1-dependent manner...
March 24, 2017: Nature Communications
Bo-Ram Cho, Ji-Sook Hahn
CK2 is a highly conserved Ser/Thr protein kinase involved in a large number of cellular processes. Here, we demonstrate that CK2-dependent phosphorylation positively regulates Msn2/4, the general stress response transcriptional activators in Saccharomyces cerevisiae, in response to various types of environmental stress conditions. CK2 overexpression elicits hyperactivation of Msn2/4, whereas deletion of one of the CK2 catalytic subunits, especially CKA2, leads to reduced transcriptional activity of Msn2/4 in response to glucose starvation, H2O2, and lactic acid...
June 2017: Biochimica et Biophysica Acta
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