scholarly journals The Protein Kinase Snf1 Is Required for Tolerance to the Ribonucleotide Reductase Inhibitor Hydroxyurea

2004 ◽  
Vol 24 (6) ◽  
pp. 2560-2572 ◽  
Author(s):  
Caroline Dubacq ◽  
Anne Chevalier ◽  
Carl Mann
Keyword(s):  
Ribonucleotide Reductase ◽  
Stress Responses ◽  
Cellular Response ◽  
Kinase Activity ◽  
Carbon Sources ◽  
Optimal Growth ◽  
Genotoxic Stress ◽  
Snf1 Kinase ◽  
Wide Range ◽  
High Level

ABSTRACT The Snf1/AMP-activated kinases are involved in a wide range of stress responses in eukaryotic cells. We discovered a novel role for the Snf1 kinase in the cellular response to genotoxic stress in yeast. snf1 mutants are hypersensitive to hydroxyurea (HU), methyl-methane sulfonate, and cadmium, but they are not sensitive to several other genotoxic agents. HU inhibits ribonucleotide reductase (RNR), and deletion of SNF1 also increased the growth defects of an rnr4 ribonucleotide reductase mutant. The snf1 mutant has a functional checkpoint response to HU insofar as cells arrest division normally and derepress the transcription of RNR genes. The sensitivity of snf1 to HU or to RNR4 deletion may be due to posttranscriptional defects in RNR function or to defects in the repair of, and recovery from, stalled replication forks. The Mig3 repressor was identified as one target of Snf1 in this pathway. Genetic and biochemical analyses suggest that a weak kinase activity is sufficient to confer resistance to HU, whereas a high level of kinase activity is required for optimal growth on carbon sources other than glucose. Quantitative regulation of Snf1 kinase activity may contribute to the specificity of the effector responses that it controls.

scholarly journals Fervidobacterium changbaicum sp. nov., a novel thermophilic anaerobic bacterium isolated from a hot spring of the Changbai Mountains, China

2007 ◽  
Vol 57 (10) ◽  
pp. 2333-2336 ◽  
Author(s):  
Jingang Cai ◽  
Yanping Wang ◽  
Dongbo Liu ◽  
Yan Zeng ◽  
Yanfen Xue ◽  
...  
Keyword(s):  
Hot Spring ◽  
Cell Envelope ◽  
Carbon Sources ◽  
Optimal Growth ◽  
Changbai Mountains ◽  
Rrna Gene ◽  
High Concentration ◽  
Gene Sequence Analysis ◽  
Wide Range ◽  
Bacterium Strain

A thermophilic, obligately anaerobic, rod-shaped bacterium (strain CBS-1T) was isolated from a hot spring mixture of water and mud of the Changbai Mountains, China. Strain CBS-1T was found to be non-sporulating, Gram-negative, with optimal growth at 75–80 °C. It grew on a wide range of carbon sources, including glucose, lactose, maltose, starch, sorbitol and pyruvate amongst others. The DNA G+C content of strain CBS-1T was 31.9 mol%. The 16S rRNA gene sequence analysis indicated that the strain was a member of the genus Fervidobacterium. The high concentration of C16 : 0 (52.2 %) in the fatty acid profile of the cell envelope supported its inclusion as a member of the genus Fervidobacterium. On the basis of the low values of DNA–DNA hybridization (25.8 and 20.5 %) and phenotypic features, strain CBS-1T represents a novel species of the genus Fervidobacterium, for which the name Fervidobacterium changbaicum sp. nov. is proposed. The type strain is CBS-1T (=DSM 17883T=JCM 13353T).

scholarly journals Aromatic Hydrocarbon Removal by Novel Extremotolerant Exophiala and Rhodotorula Spp. from an Oil Polluted Site in Mexico

2020 ◽  
Vol 6 (3) ◽  
pp. 135 ◽  
Author(s):  
Martín R. Ide-Pérez ◽  
Maikel Gilberto Fernández-López ◽  
Ayixon Sánchez-Reyes ◽  
Alfonso Leija ◽  
Ramón Alberto Batista-García ◽  
...  
Keyword(s):  
Aromatic Hydrocarbons ◽  
Aromatic Compounds ◽  
High Salinity ◽  
Polyaromatic Hydrocarbons ◽  
Carbon Sources ◽  
Optimal Growth ◽  
Polluted Site ◽  
Removal Capacity ◽  
Wide Range ◽  
Hydrocarbon Removal

Since Aromatic hydrocarbons are recalcitrant and toxic, strategies to remove them are needed. The aim of this work was to isolate fungi capable of using aromatic hydrocarbons as carbon sources. Two isolates from an oil polluted site in Mexico were identified through morphological and molecular markers as a novel Rhodotorula sp. and an Exophiala sp. Both strains were able to grow in a wide range of pH media, from 4 to 12, showing their optimal growth at alkaline pH’s and are both halotolerant. The Exophiala strain switched from hyphae to yeast morphotype in high salinity conditions. To the best of our knowledge, this is the first report of salt triggering dimorphism. The Rhodotorula strain, which is likely a new undescribed species, was capable of removing singled ringed aromatic compounds such as benzene, xylene, and toluene, but could not remove benzo[a] pyrene nor phenanthrene. Nevertheless, these hydrocarbons did not impair its growth. The Exophiala strain showed a different removal capacity. It could remove the polyaromatic hydrocarbons but performed poorly at removing toluene and xylene. Nevertheless, it still could grow well in the presence of the aromatic compounds. These strains could have a potential for aromatic compounds removal.

scholarly journals Regulation of p53 and MDM2 Activity by MTBP

2005 ◽  
Vol 25 (2) ◽  
pp. 545-553 ◽  
Author(s):  
Mark Brady ◽  
Nikolina Vlatković ◽  
Mark T. Boyd
Keyword(s):  
Ubiquitin Ligase ◽  
Stress Responses ◽  
Nuclear Export ◽  
Cellular Response ◽  
E3 Ubiquitin Ligase ◽  
Ring Finger ◽  
Dependent Manner ◽  
Γ Irradiation ◽  
Ubiquitin Ligase Activity ◽  
Wide Range

ABSTRACT p53 is a critical coordinator of a wide range of stress responses. To facilitate a rapid response to stress, p53 is produced constitutively but is negatively regulated by MDM2. MDM2 can inhibit p53 in multiple independent ways: by binding to its transcription activation domain, inhibiting p53 acetylation, promoting nuclear export, and probably most importantly by promoting proteasomal degradation of p53. The latter is achieved via MDM2's E3 ubiquitin ligase activity harbored within the MDM2 RING finger domain. We have discovered that MTBP promotes MDM2-mediated ubiquitination and degradation of p53 and also MDM2 stabilization in an MDM2 RING finger-dependent manner. Moreover, using small interfering RNA to down-regulate endogenous MTBP in unstressed cells, we have found that MTBP significantly contributes to MDM2-mediated regulation of p53 levels and activity. However, following exposure of cells to UV, but not γ-irradiation, MTBP is destabilized as part of the coordinated cellular response. Our findings suggest that MTBP differentially regulates the E3 ubiquitin ligase activity of MDM2 towards two of its most critical targets (itself and p53) and in doing so significantly contributes to MDM2-dependent p53 homeostasis in unstressed cells.

Jun N-terminal kinase activity and early growth-response factor-1 gene expression are down-regulated in Fanconi anemia group A lymphoblasts

Blood ◽  
2004 ◽  
Vol 103 (1) ◽  
pp. 128-132 ◽  
Author(s):  
Carlos Pipaon ◽  
Jose Antonio Casado ◽  
Juan Antonio Bueren ◽  
Jose Luis Fernandez-Luna
Keyword(s):  
Fanconi Anemia ◽  
Cellular Response ◽  
Growth Response ◽  
Kinase Activity ◽  
Genotoxic Stress ◽  
Early Growth ◽  
Response Factor ◽  
Early Growth Response ◽  
A Cells ◽  
Genotoxic Agents

Abstract Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome characterized by cellular sensitivity to genotoxic agents. In recent years, FA proteins have been associated with different molecules involved in signal transduction, which has raised the interest in FA-dependent signaling pathways. Here, we report that the c-Jun N-terminal kinase (JNK) fails to phosphorylate in response to UV radiation and treatment with mitomycin C in FA lymphoblast cells derived from type A patients (FA-A). Furthermore, defective kinase activity seems to be specific for JNK, because extracellular signal-regulated kinase (ERK) responded to the proper stimuli in FA-A cells. We also demonstrate that the early growth-response factor-1 (Egr-1), a JNK downstream target gene that is normally induced by genotoxic stress, is not upregulated in UV-treated FA-A cells. Moreover, FA-A cells are more sensitive to apoptosis than control lymphoblasts. Both JNK and Egr-1 may be part of a pathway triggered by FA proteins, because functional correction of FA-A cells by gene transfer restores, at least in part, JNK activation and Egr-1 expression after UV exposure. Together, our data suggest that activation of JNK and expression of Egr-1 gene in B lymphoblasts mediate a cellular response to genotoxic agents that may be induced by FA proteins.

scholarly journals Growth and autolysis of the kefir yeast Kluyveromyces marxianus in lactate culture

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shou-Chen Lo ◽  
Chia-Yin Yang ◽  
Dony Chacko Mathew ◽  
Chieh-Chen Huang
Keyword(s):  
Stress Responses ◽  
Kluyveromyces Marxianus ◽  
Tricarboxylic Acid Cycle ◽  
Carbon Sources ◽  
Free Fraction ◽  
Optimal Growth ◽  
Culture Conditions ◽  
Glycolysis Pathway ◽  
Cellular Stress Responses ◽  
Proteins And Peptides

AbstractKluyveromyces marxianus is a yeast that could be identified from kefir and can use a broad range of substrates, such as glucose and lactate, as carbon sources. The lactate produced in kefir culture can be a substrate for K. marxianus. However, the complexity of the kefir microbiota makes the traits of K. marxianus difficult to study. In this research, we focused on K. marxianus cultured with lactate as the sole carbon source. The optimal growth and released protein in lactate culture were determined under different pH conditions, and the LC–MS/MS-identified proteins were associated with the tricarboxylic acid cycle, glycolysis pathway, and cellular stress responses in cells, indicating that autolysis of K. marxianus had occurred under the culture conditions. The abundant glyceraldehyde-3-phosphate dehydrogenase 1 (GAP1) was cocrystallized with other proteins in the cell-free fraction, and the low transcription level of the GAP1 gene indicated that the protein abundance under autolysis conditions was dependent on protein stability. These results suggest that lactate induces the growth and autolysis of K. marxianus, releasing proteins and peptides. These findings can be fundamental for K. marxianus probiotic and kefir studies in the future.

scholarly journals TOR represses stress responses through global regulation of H3K27 trimethylation in plants

2021 ◽  
Author(s):  
Yihan Dong ◽  
Veli Vural Uslu ◽  
Alexandre Berr ◽  
Gaurav Singh ◽  
Csaba Papdi ◽  
...  
Keyword(s):  
Stress Responses ◽  
In Silico ◽  
In Silico Analysis ◽  
Tor Signaling ◽  
Chromatin Domains ◽  
Transcriptional Reprogramming ◽  
Wide Range ◽  
High Level ◽  
External Stimuli

Combinations of epigenetic modifications H3K4me3 and H3K27me3 implicate bistable feature which alternates between on and off state allowing rapid transcriptional changes upon external stimuli. Target of Rapamycin (TOR) functions as a central sensory hub to link a wide range of external stimuli to gene expression. However, the mechanisms underlying stimulus-specific transcriptional reprogramming by TOR remains elusive. Our in silico analysis in Arabidopsis demonstrates that TOR-repressed genes are associated with either bistable or silent chromatin domains. Both domains regulated by TOR signaling pathway are associated with high level of H3K27me3 deposited by CURLY LEAF (CLF) in specific context with LIKE HETEROCHROMATIN PROTEIN1 (LHP1). Chromatin remodeler SWI2/SNF2 ATPase BRAHMA (BRM) activates TOR-repressed genes only at bistable chromatin domains to rapidly induce biotic stress responses. Here we demonstrated both in silico and in vivo that TOR represses transcriptional stress responses through global maintenance of H3K27me3.

scholarly journals Protein phosphatase 5 and the tumor suppressor p53 down-regulate each other's activities in mice

2018 ◽  
Vol 293 (47) ◽  
pp. 18218-18229 ◽  
Author(s):  
Jun Wang ◽  
Tao Shen ◽  
Wuqiang Zhu ◽  
Longyu Dou ◽  
Hao Gu ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Protein Phosphatase ◽  
Cellular Response ◽  
Kinase Inhibitor ◽  
Genotoxic Stress ◽  
Feedback Mechanism ◽  
Protein Phosphatase 5 ◽  
Wide Range ◽  
And Function ◽  
Deficient Mice

Protein phosphatase 5 (PP5), a serine/threonine phosphatase, has a wide range of biological functions and exhibits elevated expression in tumor cells. We previously reported that pp5-deficient mice have altered ataxia-telangiectasia mutated (ATM)-mediated signaling and function. However, this regulation was likely indirect, as ATM is not a known PP5 substrate. In the current study, we found that pp5-deficient mice are hypersensitive to genotoxic stress. This hypersensitivity was associated with the marked up-regulation of the tumor suppressor tumor protein p53 and its downstream targets cyclin-dependent kinase inhibitor 1A (p21), MDM2 proto-oncogene (MDM2), and phosphatase and tensin homolog (PTEN) in pp5-deficient tissues and cells. These observations suggested that PP5 plays a role in regulating p53 stability and function. Experiments conducted with p53+/−pp5+/− or p53+/−pp5−/− mice revealed that complete loss of PP5 reduces tumorigenesis in the p53+/− mice. Biochemical analyses further revealed that PP5 directly interacts with and dephosphorylates p53 at multiple serine/threonine residues, resulting in inhibition of p53-mediated transcriptional activity. Interestingly, PP5 expression was significantly up-regulated in p53-deficient cells, and further analysis of pp5 promoter activity revealed that p53 strongly represses PP5 transcription. Our results suggest a reciprocal regulatory interplay between PP5 and p53, providing an important feedback mechanism for the cellular response to genotoxic stress.

scholarly journals TOR Complex 2- independent mutations in the regulatory PIF pocket of Gad8AKT1/SGK1 define separate branches of the stress response mechanisms in fission yeast

PLoS Genetics ◽  
2020 ◽  
Vol 16 (11) ◽  
pp. e1009196
Author(s):  
Emese Pataki ◽  
Luba Simhaev ◽  
Hamutal Engel ◽  
Adiel Cohen ◽  
Martin Kupiec ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Stress Responses ◽  
Kinase Activity ◽  
Phosphorylation Site ◽  
Genotoxic Stress ◽  
Stress Conditions ◽  
Developmental Processes ◽  
Agc Kinases ◽  
Separate Branch

The Target of rapamycin (TOR) protein kinase forms part of TOR complex 1 (TORC1) and TOR complex 2 (TORC2), two multi-subunit protein complexes that regulate growth, proliferation, survival and developmental processes by phosphorylation and activation of AGC-family kinases. In the fission yeast, Schizosaccharomyces pombe, TORC2 and its target, the AGC kinase Gad8 (an orthologue of human AKT or SGK1) are required for viability under stress conditions and for developmental processes in response to starvation cues. In this study, we describe the isolation of gad8 mutant alleles that bypass the requirement for TORC2 and reveal a separation of function of TORC2 and Gad8 under stress conditions. In particular, osmotic and nutritional stress responses appear to form a separate branch from genotoxic stress responses downstream of TORC2-Gad8. Interestingly, TORC2-independent mutations map into the regulatory PIF pocket of Gad8, a highly conserved motif in AGC kinases that regulates substrate binding in PDK1 (phosphoinositide dependent kinase-1) and kinase activity in several AGC kinases. Gad8 activation is thought to require a two-step mechanism, in which phosphorylation by TORC2 allows further phosphorylation and activation by Ksg1 (an orthologue of PDK1). We focus on the Gad8-K263C mutation and demonstrate that it renders the Gad8 kinase activity independent of TORC2 in vitro and independent of the phosphorylation sites of TORC2 in vivo. Molecular dynamics simulations of Gad8-K263C revealed abnormal high flexibility at T387, the phosphorylation site for Ksg1, suggesting a mechanism for the TORC2-independent Gad8 activity. Significantly, the K263 residue is highly conserved in the family of AGC-kinases, which may suggest a general way of keeping their activity in check when acting downstream of TOR complexes.

scholarly journals Growth and Autolysis of Kluyveromyces Marxianus Stimulated with Lactate Provides Insights into Symbiosis

2021 ◽  
Author(s):  
Shou-Chen Lo ◽  
Chia-Yin Yang ◽  
Dony Mathew ◽  
Chieh-Chen Huang
Keyword(s):  
Stress Responses ◽  
Kluyveromyces Marxianus ◽  
Tricarboxylic Acid Cycle ◽  
Carbon Sources ◽  
Free Fraction ◽  
Optimal Growth ◽  
Culture Conditions ◽  
Glycolysis Pathway ◽  
Cellular Stress Responses ◽  
Proteins And Peptides

Abstract Kluyveromyces marxianus is a yeast that was identified from kefir and can use a broad range of substrates, such as glucose and lactate, as carbon sources. The lactate produced in kefir culture can be a substrate for K. marxianus. However, the complexity of the kefir microbiota makes the traits of K. marxianus difficult to study. In this research, we focused on K. marxianus cultured with lactate as the sole carbon source. The optimal growth and released protein in lactate culture were determined under different pH conditions, and the LC-MS/MS-identified proteins were associated with the tricarboxylic acid cycle, glycolysis pathway, and cellular stress responses in cells, indicating that autolysis of K. marxianus had occurred under the culture conditions. The abundant glyceraldehyde-3-phosphate dehydrogenase (GAP1) was crystallized in the cell-free fraction, and the low transcription level of the GAP1 gene indicated that the protein abundance under autolysis conditions was dependent on protein stability. These results suggest that lactate produced by lactic acid bacteria stimulates the growth and autolysis of K. marxianus, releasing proteins and peptides. These findings can be fundamental for K. marxianus probiotic and kefir studies in the future.

The way of value of Correlation of genomic DNA microsatellite loci and live weight of Chukchi reindeer

2020 ◽  
pp. 27-32
Author(s):  
V. Dodokhov ◽  
N. Pavlova ◽  
T. Rumyantseva ◽  
L. Kalashnikova
Keyword(s):  
Microsatellite Markers ◽  
Agricultural Production ◽  
Live Weight ◽  
Biodiversity Loss ◽  
Tribal Community ◽  
High Germination ◽  
Wide Range ◽  
The Mean ◽  
High Level ◽  
Dna Microsatellite

The article presents the genetic characteristic of the Chukchi reindeer breed. The object of the study was of the Chukchi reindeer. In recent years, the number of reindeer of the Chukchi breed has declined sharply. Reduced reindeer numbers could lead to biodiversity loss. The Chukchi breed of deer has good meat qualities, has high germination viability and is adapted in adverse tundra conditions of Yakutia. Herding of the Chukchi breed of deer in Yakutia are engaged only in the Nizhnekolymsky district. There are four generic communities and the largest of which is the agricultural production cooperative of nomadic tribal community «Turvaurgin», which was chosen to assess the genetic processes of breed using microsatellite markers: Rt6, BMS1788, Rt 30, Rt1, Rt9, FCB193, Rt7, BMS745, C 143, Rt24, OheQ, C217, C32, NVHRT16, T40, C276. It was found that microsatellite markers have a wide range of alleles and generally have a high informative value for identifying of genetic differences between animals and groups of animal. The number of identified alleles is one of the indicators of the genetic diversity of the population. The total number of detected alleles was 127. The Chukchi breed of deer is characterized by a high level of heterozygosity, and the random crossing system prevails over inbreeding in the population. On average, there were 7.9 alleles (Na) per locus, and the mean number of effective alleles (Ne) was 4.1. The index of fixation averaged 0.001. The polymorphism index (PIC) ranged from 0.217 to 0.946, with an average of 0.695.

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