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ATP sulfurylase atypical leucine zipper interacts with Cys3 and calcineurin A in the regulation of sulfur amino acid biosynthesis in Cryptococcus neoformans.
da Silva JP
,
Meneghini MR
,
Santos RS
,
Alves VL
,
da Cruz Martho KF
,
Vallim MA
,
Pascon RC
.
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Fungal pathogens are a major cause of death, especially among immunocompromised patients. Therapies against invasive fungal infections are restricted to a few antifungals; therefore, novel therapies are necessary. Nutritional signaling and regulation are important for pathogen establishment in the host. In Cryptococcus neoformans, the causal agent of fungal meningitis, amino acid uptake and biosynthesis are major aspects of nutritional adaptation. Disruptions in these pathways lead to virulence attenuation in an animal model of infection, especially for sulfur uptake and sulfur amino acid biosynthesis. Deletion of Cys3, the main transcription factor that controls these pathways, is the most deleterious gene knockout in vitro and in vivo, making it an important target for further application. Previously, we demonstrated that Cys3 is part of a protein complex, including calcineurin, which is necessary to maintain high Cys3 protein levels during sulfur uptake and sulfur amino acid biosynthesis. In the current study, other aspects of Cys3 regulation are explored. Two lines of evidence suggest that C. neoformans Cys3 does not interact with the F-box WD40 protein annotated as Met30, indicating another protein mediates Cys3 ubiquitin degradation. However, we found another level of Cys3 regulation, which involves protein interactions between Cys3 and ATP sulfurylase (MET3 gene). We show that an atypical leucine zipper at the N-terminus of ATP sulfurylase is essential for physical interaction with Cys3 and calcineurin. Our data suggests that Cys3 and ATP sulfurylase interact to regulate Cys3 transcriptional activity. This work evidences the complexity involved in the regulation of a transcription factor essential for the sulfur metabolism, which is a biological process important to nutritional adaptation, oxidative stress response, nucleic acid stability, and methylation. This information may be useful in designing novel therapies against fungal infections.
Amich,
mSphere of Influence: the Importance of Metabolism for Pathogen Adaptation to Host-Imposed Stresses.
2019, Pubmed
Amich,
mSphere of Influence: the Importance of Metabolism for Pathogen Adaptation to Host-Imposed Stresses.
2019,
Pubmed
Amich,
Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant.
2016,
Pubmed
Blaiseau,
Met31p and Met32p, two related zinc finger proteins, are involved in transcriptional regulation of yeast sulfur amino acid metabolism.
1997,
Pubmed
Brunson,
Identification of residues in the WD-40 repeat motif of the F-box protein Met30p required for interaction with its substrate Met4p.
2005,
Pubmed
Calvete,
Amino acid permeases in Cryptococcus neoformans are required for high temperature growth and virulence; and are regulated by Ras signaling.
2019,
Pubmed
,
Echinobase
Davidson,
A PCR-based strategy to generate integrative targeting alleles with large regions of homology.
2002,
Pubmed
Dickinson,
Engineering the Caenorhabditis elegans genome using Cas9-triggered homologous recombination.
2013,
Pubmed
Fan,
Multiple Applications of a Transient CRISPR-Cas9 Coupled with Electroporation (TRACE) System in the Cryptococcus neoformans Species Complex.
2018,
Pubmed
Fu,
cys-3, the positive-acting sulfur regulatory gene of Neurospora crassa, encodes a protein with a putative leucine zipper DNA-binding element.
1989,
Pubmed
,
Echinobase
Görlach,
Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in Cryptococcus neoformans.
2000,
Pubmed
Hatzfeld,
Functional characterization of a gene encoding a fourth ATP sulfurylase isoform from Arabidopsis thaliana.
2000,
Pubmed
Kumar,
The sulfur controller-2 negative regulatory gene of Neurospora crassa encodes a protein with beta-transducin repeats.
1995,
Pubmed
Kumar,
An additional role for the F-box motif: gene regulation within the Neurospora crassa sulfur control network.
1998,
Pubmed
Lee,
Methionine restriction and life-span control.
2016,
Pubmed
Lev,
The Crz1/Sp1 transcription factor of Cryptococcus neoformans is activated by calcineurin and regulates cell wall integrity.
2012,
Pubmed
Li,
Structure of calcineurin in complex with PVIVIT peptide: portrait of a low-affinity signalling interaction.
2007,
Pubmed
Li,
Balanced interactions of calcineurin with AKAP79 regulate Ca2+-calcineurin-NFAT signaling.
2012,
Pubmed
Lin,
Transformation of Cryptococcus neoformans by electroporation using a transient CRISPR-Cas9 expression (TRACE) system.
2020,
Pubmed
Livak,
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
2001,
Pubmed
Logan,
Cloning of a cDNA encoded by a member of the Arabidopsis thaliana ATP sulfurylase multigene family. Expression studies in yeast and in relation to plant sulfur nutrition.
1996,
Pubmed
Martho,
The Glycerol Phosphatase Gpp2: A Link to Osmotic Stress, Sulfur Assimilation and Virulence in Cryptococcus neoformans.
2019,
Pubmed
,
Echinobase
Marzluf,
Molecular genetics of sulfur assimilation in filamentous fungi and yeast.
1997,
Pubmed
Menant,
Determinants of the ubiquitin-mediated degradation of the Met4 transcription factor.
2006,
Pubmed
Minois,
Polyamines in aging and disease.
2011,
Pubmed
Natorff,
The Aspergillus nidulans metR gene encodes a bZIP protein which activates transcription of sulphur metabolism genes.
2003,
Pubmed
Nazi,
Role of homoserine transacetylase as a new target for antifungal agents.
2007,
Pubmed
Nguyen,
Identification and characterization of a sulfite reductase gene and new insights regarding the sulfur-containing amino acid metabolism in the basidiomycetous yeast Cryptococcus neoformans.
2021,
Pubmed
Paietta,
Production of the CYS3 regulator, a bZIP DNA-binding protein, is sufficient to induce sulfur gene expression in Neurospora crassa.
1992,
Pubmed
Paietta,
Molecular cloning and analysis of the scon-2 negative regulatory gene of Neurospora crassa.
1990,
Pubmed
Pascon,
Cryptococcus neoformans methionine synthase: expression analysis and requirement for virulence.
2004,
Pubmed
Patel,
Molecular basis of AKAP79 regulation by calmodulin.
2017,
Pubmed
Patron,
Sulfate assimilation in eukaryotes: fusions, relocations and lateral transfers.
2008,
Pubmed
Rajakumar,
Impairment of MET transcriptional activators, MET4 and MET31 induced lipid accumulation in Saccharomyces cerevisiae.
2020,
Pubmed
Ren,
DOG 1.0: illustrator of protein domain structures.
2009,
Pubmed
Roje,
S-Adenosyl-L-methionine: beyond the universal methyl group donor.
2006,
Pubmed
Sadhu,
Multiple inputs control sulfur-containing amino acid synthesis in Saccharomyces cerevisiae.
2014,
Pubmed
Schröder,
Human PAPS synthase isoforms are dynamically regulated enzymes with access to nucleus and cytoplasm.
2012,
Pubmed
Skowyra,
RNA interference in Cryptococcus neoformans.
2012,
Pubmed
Thomas,
Metabolism of sulfur amino acids in Saccharomyces cerevisiae.
1997,
Pubmed
Toh-E,
Novel biosynthetic pathway for sulfur amino acids in Cryptococcus neoformans.
2018,
Pubmed
Toh-E,
Positional cloning in Cryptococcus neoformans and its application for identification and cloning of the gene encoding methylenetetrahydrofolate reductase.
2015,
Pubmed
Walvekar,
Methionine at the Heart of Anabolism and Signaling: Perspectives From Budding Yeast.
2019,
Pubmed
Yang,
Molecular and genetic analysis of the Cryptococcus neoformans MET3 gene and a met3 mutant.
2002,
Pubmed
de Melo,
The regulation of the sulfur amino acid biosynthetic pathway in Cryptococcus neoformans: the relationship of Cys3, Calcineurin, and Gpp2 phosphatases.
2019,
Pubmed
,
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