scholarly journals Genetic interaction between RLM1 and F-box motif encoding gene SAF1 contributes to stress response in Saccharomyces cerevisiae

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Meenu Sharma ◽  
V. Verma ◽  
Narendra K. Bairwa
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Stress Response ◽  
Stress Tolerance ◽  
Experimental Analysis ◽  
Genetic Interaction ◽  
Cellular Growth ◽  
Genome Database ◽  
Transcription Regulators ◽  
Adenine Deaminase

Abstract Background Stress response is mediated by the transcription of stress-responsive genes. The F-box motif protein Saf1p is involved in SCF-E3 ligase mediated degradation of the adenine deaminase, Aah1p upon nutrient stress. The four transcription regulators, BUR6, MED6, SPT10, SUA7, are listed for SAF1 in the genome database of Saccharomyces cerevisiae. Here in this study, we carried out an in-silico analysis of gene expression and transcription factor databases to understand the regulation of SAF1 expression during stress for hypothesis and experimental analysis. Result An analysis of the GEO profile database indicated an increase in SAF1 expression when cells were treated with stress agents such as Clioquinol, Pterostilbene, Gentamicin, Hypoxia, Genotoxic, desiccation, and heat. The increase in expression of SAF1 during stress conditions correlated positively with the expression of RLM1, encoding the Rlm1p transcription factor. The expression of AAH1 encoding Aah1p, a Saf1p substrate for ubiquitination, appeared to be negatively correlated with the expression of RLM1 as revealed by an analysis of the Yeastract expression database. Based on analysis of expression profile and regulatory association of SAF1 and RLM1, we hypothesized that inactivation of both the genes together may contribute to stress tolerance. The experimental analysis of cellular growth response of cells lacking both SAF1 and RLM1 to selected stress agents such as cell wall and osmo-stressors, by spot assay indicated stress tolerance phenotype similar to parental strain however sensitivity to genotoxic and microtubule depolymerizing stress agents. Conclusions Based on in-silico and experimental data we suggest that SAF1 and RLM1 both interact genetically in differential response to genotoxic and general stressors.

scholarly journals Genetic Interaction between RLM1 and F-box Motif Encoding gene SAF1 Contributes to Stress Response in Saccharomyces cerevisiae

2019 ◽  
Author(s):  
Meenu Sharma ◽  
V. Verma ◽  
Narendra K Bairwa
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Stress Response ◽  
Experimental Analysis ◽  
Genetic Interaction ◽  
Cellular Growth ◽  
Calcofluor White ◽  
Genome Database ◽  
Adenine Deaminase

AbstractStress response is mediated by transcription of stress responsive genes. F-box motif protein Saf1 involves in SCF-E3 ligase mediated degradation of the adenine deaminase, Aah1 upon nutrient stress. Four transcription regulators, BUR6, MED6, SPT10, SUA7, have been reported for SAF1 gene in genome database of Saccharomyces cerevisiae. Here in this study an in-silco analysis of gene expression and transcription factor databases was carried out to understand the regulation of SAF1 gene expression during stress for hypothesis generation and experimental analysis. The GEO profile database analysis showed increased expression of SAF1 gene when treated with clioquinol, pterostilbene, gentamicin, hypoxia, genotoxic, desiccation, and heat stress, in WT cells. SAF1 gene expression in stress conditions correlated positively whereas AAH1 expression negatively with RLM1 transcription factor, which was not reported earlier. Based on analysis of expression profile and regulatory association of SAF1 and RLM1, we hypothesized that inactivation of both the genes may contribute to stress tolerance. The experimental analysis with the double mutant, saf1Δrlm1Δ for cellular growth response to stress causing agents, showed tolerance to calcofluor white, SDS, and hydrogen peroxide. On the contrary, saf1Δrlm1Δ showed sensitivity to MMS, HU, DMSO, Nocodazole, Benomyl stress. Based on in-silico and experimental data we suggest that SAF1 and RLM1 both interact genetically in differential response to genotoxic and general stressors.

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 Transcriptional Responses to ppGpp and DksA

2018 ◽  
Vol 72 (1) ◽  
pp. 163-184 ◽  
Author(s):  
Richard L. Gourse ◽  
Albert Y. Chen ◽  
Saumya Gopalkrishnan ◽  
Patricia Sanchez-Vazquez ◽  
Angela Myers ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stress Response ◽  
Rna Polymerase ◽  
Stringent Response ◽  
Signaling Molecules ◽  
Nutrient Deprivation ◽  
Secondary Channel ◽  
Transcriptional Responses ◽  
Transcription Regulators ◽  
Bacterial Domain

The stringent response to nutrient deprivation is a stress response found throughout the bacterial domain of life. Although first described in proteobacteria for matching ribosome synthesis to the cell's translation status and for preventing formation of defective ribosomal particles, the response is actually much broader, regulating many hundreds of genes—some positively, some negatively. Utilization of the signaling molecules ppGpp and pppGpp for this purpose is ubiquitous in bacterial evolution, although the mechanisms employed vary. In proteobacteria, the signaling molecules typically bind to two sites on RNA polymerase, one at the interface of the β′ and ω subunits and one at the interface of the β′ secondary channel and the transcription factor DksA. The β′ secondary channel is targeted by other transcription regulators as well. Although studies on the transcriptional outputs of the stringent response date back at least 50 years, the mechanisms responsible are only now coming into focus.

scholarly journals Transcription Factor CaSBP12 Negatively Regulates Salt Stress Tolerance in Pepper (Capsicum annuum L.)

2020 ◽  
Vol 21 (2) ◽  
pp. 444
Author(s):  
Huai-Xia Zhang ◽  
Wen-Chao Zhu ◽  
Xiao-Hui Feng ◽  
Jing-Hao Jin ◽  
Ai-Min Wei ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Salt Stress ◽  
Stress Tolerance ◽  
Severity Index ◽  
Pepper Plant ◽  
Plant Tolerance ◽  
Salt Stress Tolerance ◽  
Genome Database ◽  
Transcription Factor Genes ◽  
Pepper Genome

SBP-box (Squamosa-promoter binding protein) genes are a type of plant-specific transcription factor and play important roles in plant growth, signal transduction, and stress response. However, little is known about the role of pepper SBP-box transcription factor genes in response to abiotic stress. Here, one of the pepper SBP-box gene, CaSBP12, was selected and isolated from pepper genome database in our previous study. The CaSBP12 gene was induced under salt stress. Silencing the CaSBP12 gene enhanced pepper plant tolerance to salt stress. The accumulation of reactive oxygen species (ROS) of the detached leaves of CaSBP12-silenced plants was significantly lower than that of control plants. Besides, the Na+, malondialdehyde content, and conductivity were significantly increased in control plants than that in the CaSBP12-silenced plants. In addition, the CaSBP12 over-expressed Nicotiana benthamiana plants were more susceptible to salt stress with higher damage severity index percentage and accumulation of ROS as compared to the wild-type. These results indicated that CaSBP12 negatively regulates salt stress tolerance in pepper may relate to ROS signaling cascades.

BCL6 Mediates a Stress Tolerance Phenotype through Its BTB Domain

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 567-567 ◽  
Author(s):  
Tharu M Fernando ◽  
Shao Ning Yang ◽  
Chuanxin Huang ◽  
Gabriela Chiosis ◽  
Leandro Cerchietti ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stress Response ◽  
B Cells ◽  
Heat Shock ◽  
Growth Inhibition ◽  
B Cell ◽  
Stress Tolerance ◽  
Cell Lines ◽  
Btb Domain ◽  
High Affinity

Abstract Diffuse large B-cell lymphomas (DLBCLs) arise from germinal center (GC) B-cells. Normal GC B-cells clonally expand and undergo somatic hypermutation of their immunoglobulin loci to produce high-affinity antibodies. Induction of BCL6, a transcription factor that represses genes involved in DNA damage sensing and checkpoint activation, is essential for GC B-cells to tolerate replicative and genotoxic stress without inducing cell cycle arrest. We previously showed that BCL6 forms a complex with tumor enriched HSP90 (TE-HSP90) to repress target genes in DLBCL cells. Based on these facts, we hypothesized that BCL6 is a component of a conserved stress response program, required for GC formation and maintenance of established lymphoma cells. Along these lines, we report that treatment of mice with TE-HSP90-selective inhibitor PU-H71 completely abrogates GC formation after immunization by T-cell dependent antigen. Stress responses are coordinated by the transcription factor heat shock factor 1 (HSF1), which is activated by phosphorylation. Immunofluorescence of human tonsillar sections revealed HSF1-pSer326-positive cells within BCL6+ GC B-cells. We found that HSF1-/- mice manifest a 40% decrease in GC B-cells after immunization and significantly (p=0.0073) decreased titers of high-affinity immunoglobulin compared to WT mice, indicating defective affinity maturation. Mixed chimera experiments revealed that the GC defect is exclusively due to malfunction of GC B-cells and not other cell types. Because of this GC B-cell defect, we reasoned that HSF1 might induce BCL6 expression. We identified three conserved heat shock elements (HSEs) in the BCL6 promoter. Quantitative ChIP analysis demonstrated HSF1 binding to these HSEs in human GC B-cells. Heat shock induced the BCL6 promoter in reporter assays and resulted in an increase in BCL6 nascent transcripts and protein. However this induction did not occur in HSF1-/-B-cells or after HSF1 knockdown. These data suggest that BCL6 is a stress response gene downstream of HSF1. To determine whether BCL6 is involved in mediating a stress tolerant phenotype, we performed serial stress response assays (using heat shock) in B220+ splenocytes from BCL6+/+ or BCL6-/- mice. Whereas BCL6+/+ cells were able acquire stress tolerance if preconditioned with an initial heat shock, BCL6-/- splenocytes failed to adapt to stress and died. To understand the mechanistic basis of this finding, we generated knockin mice with point mutations that disrupt the repressor activity of the BCL6 BTB (BCL6BTB) or the BCL6 RD2 (BCL6RD2) domain. Interestingly while splenocytes from BCL6RD2 mutant mice displayed normal stress tolerance responses, BCL6BTB mutant B-cells were completely deficient similar to BCL6-/-B-cells. Likewise the BCL6 BTB domain inhibitor RI-BPI also abrogated the BCL6 stress tolerance function. DLBCLs are dependent on many of the same molecular mechanisms as normal GC B-cells (e.g. BCL6). Indeed the lentiviral transduction of HSF1 shRNAs in DLBCL cell lines reduced BCL6 protein levels by more than 50% resulting in a 70%-90% loss in viability. HSF1 is known to help tumor cells survive exposure to chemotherapy drugs, and the BCL6 BTB domain is required for stress tolerance. Thus we hypothesized that BCL6 BTB domain targeted therapy (RI-BPI) would synergistically kill DLBCL when combined with chemotherapy. We treated 7 DLBCL cell lines with RI-BPI in combination with doxorubicin, vincristine, dexamethasone, mechlorethamine (in place of cyclophosphamide), and their combination CHOP. Almost all combinations resulted in an additive or synergistic effect on DLBCL growth inhibition. Moreover the combination of RI-BPI and doxorubicin in a DBLCL xenograft model was more potent and significantly (p<0.001) better at reducing tumor growth than either drug alone. Using an ex vivo coculture system for primary human DLBCL specimens, the combination of RI-BPI and CHOP had at least an additive effect on growth inhibition in 80% of primary human DLBCL cells with the majority demonstrating a synergistic anti-lymphoma effect. Collectively we demonstrate that BCL6 is an HSF1-dependent stress tolerance factor and mediates this effect via its BTB domain. This phenomenon occurs during normal GC formation and in lymphoma cells. Thus targeting the BTB domain of BCL6 pharmacologically in combination with other chemotherapy is a viable strategy to eradicate lymphomas. Disclosures No relevant conflicts of interest to declare.

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