ArticleMolecular microbiology2019
Calcineurin-dependent dephosphorylation of the transcription factor CrzA at specific sites controls conidiation, stress tolerance, and virulence of Aspergillus fumigatus.
Article in Molecular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Nootkatone antifungal activity and calcium signaling-mediated resistance in Aspergillus fumigatus.Applied microbiology and biotechnology · 2026Article
- Transcription factors SltA and CrzA reversely regulate calcium homeostasis under calcium-limited conditions.Applied and environmental microbiology · 2023Article
- Molecular Dissection of Crz1 and Its Dynamic Subcellular Localization inJournal of fungi (Basel, Switzerland) · 2023Article
- Calcineurin Inhibitor CN585 Exhibits Off-Target Effects in the Human Fungal PathogenJournal of fungi (Basel, Switzerland) · 2022Article
- Potential Antifungal Targets forInternational journal of molecular sciences · 2022Review
- Article
- Protein Kinase A Regulates Autophagy-Associated Proteins Impacting Growth and Virulence ofJournal of fungi (Basel, Switzerland) · 2022Article
- TheFrontiers in microbiology · 2022Article
- The metal chaperone protein MtmA plays important roles in antifungal drug susceptibility inFrontiers in microbiology · 2022Article
- Article
- Article
- The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis inmBio · 2020Article
- CRZ1 regulator and calcium cooperatively modulate holocellulases gene expression in Trichoderma reesei QM6a.Genetics and molecular biology · 2020Article
- Function ofToxins · 2019Article
- Calcineurin A Is Essential in the Regulation of Asexual Development, Stress Responses and Pathogenesis inFrontiers in microbiology · 2019Article
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Authors and funding
8 authors.
Funding
Abstract
Calcium signaling through calcineurin and its major transcription factor (TF), CrzA, is integral to hyphal growth, stress response and virulence of the pathogenic fungus Aspergillus fumigatus, the leading etiology of invasive aspergillosis. Dephosphorylation of CrzA by calcineurin activates the TF, but the specific phosphorylation sites and their roles in the activation/inactivation mechanism are unknown. Mass spectroscopic analysis identified 20 phosphorylation sites, the majority of which were specific to filamentous fungi and distributed throughout the CrzA protein, with particular concentration in a serine-rich region N-terminal to the conserved DNA-binding domain (DBD). Site-directed mutagenesis of phosphorylated residues revealed that CrzA activity during calcium stimulation can only be suppressed by a high degree of phosphorylation in multiple regions of the protein. Our findings further suggest that this regulation is not solely accomplished through control of CrzA nuclear import. Additionally, we demonstrate the importance of the CrzA phosphorylation state in regulating growth, conidiation, calcium and cell wall stress tolerance, and virulence. Finally, we identify two previously undescribed nuclear localization sequences in the DBD. These findings provide novel insight into the phosphoregulation of CrzA which may be exploited to selectively target A. fumigatus.
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