ArticleMolecular microbiology2009
Cryptococcus neoformans Site-2 protease is required for virulence and survival in the presence of azole drugs.
Article in Molecular microbiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 62 citations in OpenAlex.
- Functional Characterization of a Signal Peptide Peptidase inInternational journal of molecular sciences · 2026Article
- Comparative Transcriptomic Analyses Reveal Potential Stp1 Regulatory Roles Independent of Sre1 inInternational journal of molecular sciences · 2025Article
- Article
- Identification of Potential New Genes Related to the SREBP Pathway inBiomolecules · 2024Article
- Natural compounds from freshwater mussels disrupt fungal virulence determinants and influence fluconazole susceptibility in the presence of macrophages inMicrobiology spectrum · 2024Article
- Novel Promising Antifungal Target Proteins for Conquering Invasive Fungal Infections.Frontiers in microbiology · 2022Review
- From Naturally-Sourced Protease Inhibitors to New Treatments for Fungal Infections.Journal of fungi (Basel, Switzerland) · 2021Review
- The SREBP (Sterol Regulatory Element-Binding Protein) pathway: a regulatory bridge between carotenogenesis and sterol biosynthesis in the carotenogenic yeast Xanthophyllomyces dendrorhous.Biological research · 2021Review
- Integrated sensing of host stresses by inhibition of a cytoplasmic two-component system controlseLife · 2021Article
- Article
- Metallopeptidase Stp1 activates the transcription factor Sre1 in the carotenogenic yeastJournal of lipid research · 2020Article
- The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors.Frontiers in microbiology · 2019Review
- Oxygen-responsive transcriptional regulation of lipid homeostasis in fungi: Implications for anti-fungal drug development.Seminars in cell & developmental biology · 2018Review
- Genome-wide analysis of the regulation of Cu metabolism in Cryptococcus neoformans.Molecular microbiology · 2018Article
- HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence.Scientific reports · 2018Article
- Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi.Molecular microbiology · 2018Review
- Article
- Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host.PloS one · 2017Article
- The Chloroplast Protease AMOS1/EGY1 Affects Phosphate Homeostasis under Phosphate Stress.Plant physiology · 2016Article
- Mga2 Transcription Factor Regulates an Oxygen-responsive Lipid Homeostasis Pathway in Fission Yeast.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
In the human fungal pathogen Cryptococcus neoformans, the SREBP orthologue Sre1 is important for adaptation and growth in nutrient-limiting host tissues. In this study, we characterize the C. neoformans serotype A Sre1 and its activating protease, Stp1. We demonstrate that Stp1 is a functionally conserved orthologue of the mammalian Site-2 protease and that Stp1 cleaves Sre1 within its predicted first transmembrane segment. Gene expression analysis revealed that Stp1 is required for both Sre1-dependent and Sre1-independent gene transcription, indicating that other substrates of Stp1 may exist. Using gas chromatography, we showed that Sre1 and Stp1 are required for both normoxic and hypoxic ergosterol biosynthesis, and therefore cells lacking SRE1 or STP1 are defective for growth in the presence of low levels of the ergosterol biosynthesis inhibitors, itraconazole and 25-thialanosterol. Importantly, our studies demonstrated fungicidal effects of itraconazole and 25-thialanosterol towards sre1Delta and stp1Delta cells, demonstrating that the Sre1 pathway is required for both growth and survival in the presence of sterol biosynthesis-inhibiting antifungal drugs. Given the need for fungicidal drugs, we propose that inhibitors of Stp1, Sre1, or other regulators of Sre1 function administered in combination with a sterol synthesis inhibitor could prove an effective anticryptococcal therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.