ArticleEukaryotic cell2003
The yeast protein kinase C cell integrity pathway mediates tolerance to the antifungal drug caspofungin through activation of Slt2p mitogen-activated protein kinase signaling.
Article in Eukaryotic cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 194 citations in OpenAlex.
- Article
- Resilience in Resistance: The Role of Cell Wall Integrity in Multidrug-Resistant Candida.Journal of fungi (Basel, Switzerland) · 2025Review
- Caspofungin paradoxical growth inFrontiers in cellular and infection microbiology · 2025Article
- Cell Wall-Mediated Antifungal Activity of the Aqueous Extract ofAntibiotics (Basel, Switzerland) · 2024Article
- Comparison of the impact of two key fungal signalling pathways on Zymoseptoria tritici infection reveals divergent contribution to invasive growth through distinct regulation of infection-associated genes.Molecular plant pathology · 2023Article
- Development of Echinocandin Resistance inJournal of fungi (Basel, Switzerland) · 2023Article
- Fungal resilience and host-pathogen interactions: Future perspectives and opportunities.Parasite immunology · 2023Review
- Antifungal discovery.Current opinion in microbiology · 2022Review
- Article
- The role ofiScience · 2022Review
- Genotypic, proteomic, and phenotypic approaches to decipher the response to caspofungin and calcineurin inhibitors in clinical isolates of echinocandin-resistant Candida glabrata.The Journal of antimicrobial chemotherapy · 2022Article
- Control of Gene Expression via the Yeast CWI Pathway.International journal of molecular sciences · 2022Review
- What 'Omics can tell us about antifungal adaptation.FEMS yeast research · 2022Review
- Article
- Article
- Differential Requirement for the Cell Wall Integrity Sensor Wsc1p in Diploids Versus Haploids.Journal of fungi (Basel, Switzerland) · 2021Article
- Cell Wall Integrity Pathway Involved in Morphogenesis, Virulence and Antifungal Susceptibility inJournal of fungi (Basel, Switzerland) · 2021Review
- Fungal Cell Wall Proteins and Signaling Pathways Form a Cytoprotective Network to Combat Stresses.Journal of fungi (Basel, Switzerland) · 2021Review
- Article
- With an Ear Up against the Wall: An Update on Mechanoperception inPlants (Basel, Switzerland) · 2021Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The echinocandin caspofungin is a new antifungal drug that blocks cell wall synthesis through inhibition of beta-(1-3)-glucan synthesis. Saccharomyces cerevisiae cells are able to tolerate rather high caspofungin concentrations, displaying high viability at low caspofungin doses. To identify yeast genes implicated in caspofungin tolerance, we performed a genome-wide microarray analysis. Strikingly, caspofungin treatment rapidly induces a set of genes from the protein kinase C (PKC) cell integrity signaling pathway, as well as those required for cell wall maintenance and architecture. The mitogen-activated protein kinase Slt2p is rapidly activated by phosphorylation, triggering signaling through the PKC pathway. Cells lacking genes such as SLT2, BCK1, and PKC1, as well as the caspofungin target gene, FKS1, display pronounced hypersensitivity, demonstrating that the PKC pathway is required for caspofungin tolerance. Notably, the cell surface integrity sensor Wsc1p, but not the sensors Wsc2-4p and Mid2p, is required for sensing caspofungin perturbations. The expression modulation of PKC target genes requires the transcription factor Rlm1p, which controls expression of several cell wall synthesis and maintenance genes. Thus, caspofungin-induced cell wall damage requires Wsc1p as a dedicated sensor to launch a protective response through the activated salvage pathway for de novo cell wall synthesis. Our results establish caspofungin as a specific activator of Slt2p stress signaling in baker's yeast.
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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.