Transcription factor GlbHLH regulates hyphal growth, stress resistance, and polysaccharide biosynthesis in Ganoderma lucidum

ABSTRACTThe yeastYarrowia lipolyticaundergoes a morphological transition from yeast-to-hyphal growth in response to environmental conditions. A forward genetic screen was used to identify mutants that reliably remain in the yeast phase, which were then assessed by whole-genome sequencing. All thesmoothmutants identified, so named because of their colony morphology, exhibit independent loss of DNA at a repetitive locus made up of interspersed ribosomal DNA and short 10- to 40-mer telomere-like repeats. The loss of repetitive DNA is associated with downregulation of genes with stress response elements (5′-CCCCT-3′) and upregulation of genes with cell cycle box (5′-ACGCG-3′) motifs in their promoter region. The stress response element is bound by the transcription factor Msn2p inSaccharomyces cerevisiae. We confirmed that theY. lipolyticamsn2(Ylmsn2) ortholog is required for hyphal growth and found that overexpression of Ylmsn2enables hyphal growth insmoothstrains. The cell cycle box is bound by the Mbp1p/Swi6p complex inS. cerevisiaeto regulate G1-to-S phase progression. We found that overexpression of either the Ylmbp1or Ylswi6homologs decreased hyphal growth and that deletion of either Ylmbp1or Ylswi6promotes hyphal growth insmoothstrains. A second forward genetic screen for reversion to hyphal growth was performed with thesmooth-33mutant to identify additional genetic factors regulating hyphal growth inY. lipolytica. Thirteen of the mutants sequenced from this screen had coding mutations in five kinases, including the histidine kinases Ylchk1and Ylnik1and kinases of the high-osmolarity glycerol response (HOG) mitogen-activated protein (MAP) kinase cascade Ylssk2, Ylpbs2, and Ylhog1. Together, these results demonstrate thatY. lipolyticatransitions to hyphal growth in response to stress through multiple signaling pathways.IMPORTANCEMany yeasts undergo a morphological transition from yeast-to-hyphal growth in response to environmental conditions. We used forward and reverse genetic techniques to identify genes regulating this transition inYarrowia lipolytica. We confirmed that the transcription factor Ylmsn2is required for the transition to hyphal growth and found that signaling by the histidine kinases Ylchk1and Ylnik1as well as the MAP kinases of the HOG pathway (Ylssk2, Ylpbs2, and Ylhog1) regulates the transition to hyphal growth. These results suggest thatY. lipolyticatransitions to hyphal growth in response to stress through multiple kinase pathways. Intriguingly, we found that a repetitive portion of the genome containing telomere-like and rDNA repeats may be involved in the transition to hyphal growth, suggesting a link between this region and the general stress response.

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Peroxiporins Are Induced Upon Oxidative Stress Insult and Are Associated with Oxidative Stress Resistance in Colon Cancer Cell Lines

Antioxidants ◽

10.3390/antiox10111856 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1856

Author(s):

Ana Čipak Gašparović ◽

Lidija Milković ◽

Claudia Rodrigues ◽

Monika Mlinarić ◽

Graça Soveral

Keyword(s):

Oxidative Stress ◽

Colon Cancer ◽

Transcription Factor ◽

Cell Lines ◽

Stress Resistance ◽

Therapy Resistance ◽

Colon Cancer Cell ◽

Colon Cancer Cell Lines ◽

Intracellular Ros ◽

Ht 29

Oxidative stress can induce genetic instability and change cellular processes, resulting in colorectal cancer. Additionally, adaptation of oxidative defense causes therapy resistance, a major obstacle in successful cancer treatment. Peroxiporins are aquaporin membrane channels that facilitate H2O2 membrane permeation, crucial for regulating cell proliferation and antioxidative defense. Here, we investigated four colon cancer cell lines (Caco-2, HT-29, SW620, and HCT 116) for their sensitivity to H2O2, cellular antioxidative status, and ROS intracellular accumulation after H2O2 treatment. The expression of peroxiporins AQP1, AQP3, and AQP5 and levels of NRF2, the antioxidant transcription factor, and PPARγ, a transcription factor that regulates lipid metabolism, were evaluated before and after oxidative insult. Of the four tested cell lines, HT-29 was the most resistant and showed the highest expression of all tested peroxiporins and the lowest levels of intracellular ROS, without differences in GSH levels, catalase activity, nor NF2 and PPARγ levels. Caco-2 shows high expression of AQP3 and similar resistance as HT-29. These results imply that oxidative stress resistance can be obtained by several mechanisms other than the antioxidant defense system. Regulation of intracellular ROS through modulation of peroxiporin expression may represent an additional strategy to target the therapy resistance of cancer cells.

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Polyamine biosynthesis and biological roles in rhizobia

FEMS Microbiology Letters ◽

10.1093/femsle/fnz084 ◽

2019 ◽

Vol 366 (7) ◽

Cited By ~ 2

Author(s):

Victor A Becerra-Rivera ◽

Michael F Dunn

Keyword(s):

Stress Resistance ◽

Biofilm Formation ◽

Sinorhizobium Meliloti ◽

Growth Stress ◽

Nitrogen Fixing ◽

Amino Groups ◽

Nitrogen Fixing Bacteria ◽

Polyamine Biosynthesis ◽

Exopolysaccharide Production

ABSTRACTPolyamines are ubiquitous molecules containing two or more amino groups that fulfill varied and often essential physiological and regulatory roles in all organisms. In the symbiotic nitrogen-fixing bacteria known as rhizobia, putrescine and homospermidine are invariably produced while spermidine and norspermidine synthesis appears to be restricted to the alfalfa microsymbiont Sinorhizobium meliloti. Studies with rhizobial mutants deficient in the synthesis of one or more polyamines have shown that these compounds are important for growth, stress resistance, motility, exopolysaccharide production and biofilm formation. In this review, we describe these studies and examine how polyamines are synthesized and regulated in rhizobia.

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The GATA transcription factor/ MTA ‐1 homolog egr‐1 promotes longevity and stress resistance in C aenorhabditis elegans

Aging Cell ◽

10.1111/acel.12179 ◽

2013 ◽

Vol 13 (2) ◽

pp. 329-339 ◽

Cited By ~ 7

Author(s):

Stephanie M. Zimmerman ◽

Stuart K. Kim

Keyword(s):

Transcription Factor ◽

Stress Resistance ◽

Gata Transcription Factor

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Agrimonia procera Wallr. Extract Increases Stress Resistance and Prolongs Life Span in Caenorhabditis elegans via Transcription Factor DAF-16 (FoxO Orthologue)

Antioxidants ◽

10.3390/antiox7120192 ◽

2018 ◽

Vol 7 (12) ◽

pp. 192 ◽

Cited By ~ 2

Author(s):

Christina Saier ◽

Inge Gommlich ◽

Volker Hiemann ◽

Sabrina Baier ◽

Karoline Koch ◽

...

Keyword(s):

Transcription Factor ◽

Caenorhabditis Elegans ◽

Life Span ◽

Stress Resistance ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Model Organism ◽

Amyloid Β ◽

Ethanol Extract

Agrimonia procera is a pharmacologically interesting plant which is proposed to protect against various diseases due to its high amount of phytochemicals, e.g., polyphenols. However, in spite of the amount of postulated health benefits, studies concerning the mechanistic effects of Agrimonia procera are limited. Using the nematode Caenorhabditis elegans, we were able to show that an ethanol extract of Agrimonia procera herba (eAE) mediates strong antioxidative effects in the nematode: Beside a strong radical-scavenging activity, eAE reduces accumulation of reactive oxygen species (ROS) accumulation and protects against paraquat-induced oxidative stress. The extract does not protect against amyloid-β-mediated toxicity, but efficiently increases the life span (up to 12.7%), as well as the resistance to thermal stress (prolongation of survival up to 22%), of this model organism. Using nematodes deficient in the forkhead box O (FoxO)-orthologue DAF-16, we were able to demonstrate that beneficial effects of eAE on stress resistance and life span were mediated via this transcription factor. We showed antioxidative, stress-reducing, and life-prolonging effects of eAE in vivo and were able to demonstrate a molecular mechanism of this extract. These results may be important for identifying further molecular targets of eAE in humans.

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Role for Endosomal and Vacuolar GTPases in Candida albicans Pathogenesis

Infection and Immunity ◽

10.1128/iai.01458-08 ◽

2009 ◽

Vol 77 (6) ◽

pp. 2343-2355 ◽

Cited By ~ 26

Author(s):

Douglas A. Johnston ◽

Karen E. Eberle ◽

Joy E. Sturtevant ◽

Glen E. Palmer

Keyword(s):

Candida Albicans ◽

Stress Resistance ◽

Double Mutant ◽

Hyphal Growth ◽

Filamentous Growth ◽

Rab Gtpases ◽

Fungal Cell ◽

Cellular Stresses ◽

Vacuole Biogenesis

ABSTRACT The vacuole has crucial roles in stress resistance and adaptation of the fungal cell. Furthermore, in Candida albicans it has been observed to undergo dramatic expansion during the initiation of hyphal growth, to produce highly “vacuolated” subapical compartments. We hypothesized that these functions may be crucial for survival within the host and tissue-invasive hyphal growth. We also considered the role of the late endosome or prevacuole compartment (PVC), a distinct organelle involved in vacuolar and endocytic trafficking. We identified two Rab GTPases, encoded by VPS21 and YPT72, required for trafficking through the PVC and vacuole biogenesis, respectively. Deletion of VPS21 or YPT72 led to mild sensitivities to some cellular stresses. However, deletion of both genes resulted in a synthetic phenotype with severe sensitivity to cellular stress and impaired growth. Both the vps21Δ and ypt72Δ mutants had defects in filamentous growth, while the double mutant was completely deficient in polarized growth. The defects in hyphal growth were not suppressed by an “active” RIM101 allele or loss of the hyphal repressor encoded by TUP1. In addition, both single mutants had significant attenuation in a mouse model of hematogenously disseminated candidiasis, while the double mutant was rapidly cleared. Histological examination confirmed that the vps21Δ and ypt72Δ mutants are deficient in hyphal growth in vivo. We suggest that the PVC and vacuole are required on two levels during C. albicans infection: (i) stress resistance functions required for survival within tissue and (ii) a role in filamentous growth which may aid host tissue invasion.

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WdStuAp, an APSES Transcription Factor, Is a Regulator of Yeast-Hyphal Transitions in Wangiella (Exophiala) dermatitidis

Eukaryotic Cell ◽

10.1128/ec.00037-07 ◽

2007 ◽

Vol 6 (9) ◽

pp. 1595-1605 ◽

Cited By ~ 16

Author(s):

Qin Wang ◽

Paul J. Szaniszlo

Keyword(s):

Transcription Factor ◽

Agar Medium ◽

Hyphal Growth ◽

Surface Growth ◽

Yeast Growth ◽

Amino Terminal ◽

Yeast Extract Peptone Dextrose ◽

Development And Differentiation ◽

Colony Surface ◽

The Rich

ABSTRACT APSES transcription factors are well-known regulators of fungal cellular development and differentiation. To study the function of an APSES protein in the fungus Wangiella dermatitidis, a conidiogenous and polymorphic agent of human phaeohyphomycosis with yeast predominance, the APSES transcription factor gene WdSTUA was cloned, sequenced, disrupted, and overexpressed. Analysis showed that its derived protein was most similar to the APSES proteins of other conidiogenous molds and had its APSES DNA-binding domain located in the amino-terminal half. Deletion of WdSTUA in W. dermatitidis induced convoluted instead of normal smooth colony surface growth on the rich yeast maintenance agar medium yeast extract-peptone-dextrose agar (YPDA) at 37°C. Additionally, deletion of WdSTUA repressed aerial hyphal growth, conidiation, and invasive hyphal growth on the nitrogen-poor, hypha-inducing agar medium potato dextrose agar (PDA) at 25°C. Ectopic overexpression of WdSTUA repressed the convoluted colony surface growth on YPDA at 37°C, and also strongly repressed hyphal growth on PDA at 25°C and 37°C. These new results provide additional insights into the diverse roles played by APSES factors in fungi. They also suggest that the transcription factor encoded by WdSTUA is both a positive and negative morphotype regulator in W. dermatitidis and possibly other of the numerous human pathogenic, conidiogenous fungi capable of yeast growth.

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