The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
The yeast protein kinase C cell integrity pathway mediates tolerance to the antifungal drug caspofungin through activation of Slt2p mitogen-activated protein kinase signaling.
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The protein kinase C (PKC) cell wall integrity pathway has a well-established function in mediating tolerance to echinocandins in S. cerevisiae [44],[45].”
From Hsp90 Governs Echinocandin Resistance in the Pathogenic Yeast Candida albicans via Calcineurin (2009) · cites this paper as [45]
Citations
Cites
Cobb, M. H., & Goldsmith, E. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.25.14843 · Cited by 1,718
A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae
Schmitt, M. E., Brown, T. A., & Trumpower, B. L. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.10.3091 · Cited by 1,344
Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF
Iyer, V. R., Horak, C. E., Scafe, C., Botstein, D., Snyder, M. P., & Brown, P. O. (2001) · Nature · doi:10.1038/35054095 · Cited by 1,084
Dynamics of cell wall structure in Saccharomyces cerevisiae
Klis, F. M., Mol, P. C., Hellingwerf, K. J., & Brul, S. (2002) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2002.tb00613.x · Cited by 1,007
Review: Cell wall assembly in yeast
Klis, F. M. (1994) · Yeast · doi:10.1002/yea.320100702 · Cited by 552
Kamada, Y., Jung, U. S., Piotrowski, J., & Levin, D. E. (1995) · Genes & Development · doi:10.1101/gad.9.13.1559 · Cited by 488
Differential Expression and Function of Two Homologous Subunits of Yeast 1,3-β-D-Glucan Synthase
Mazur, P., Morin, N. R., Baginsky, W. F., El-Sherbeini, M., Clemas, J. A., NIELSEN, J. B. K., & Foor, F. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.10.5671 · Cited by 425
Jung, U. S., & Levin, D. E. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01667.x · Cited by 422
A candidate protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle
Levin, D. E., Fields, F. O., Kunisawa, R., Bishop, J. M., & Thorner, J. W. (1990) · Cell · doi:10.1016/0092-8674(90)90360-q · Cited by 413
The contribution of cell wall proteins to the organization of the yeast cell wall
Kapteyn, J. C., ENDE, H. V. D., & Klis, F. M. (1999) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(98)00137-8 · Cited by 386
Cited by
Sorted by citations
The Fungal Cell Wall: Structure, Biosynthesis, and Function
Gow, N. A. R., Latge, J.-P., & Munro, C. A. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.funk-0035-2016 · Cited by 1,423
Cell Wall Assembly in Saccharomyces cerevisiae
Lesage, G., & Bussey, H. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00038-05 · Cited by 849
Levin, D. E. (2011) · Genetics · doi:10.1534/genetics.111.128264 · Cited by 827
Mechanisms of Antifungal Drug Resistance
Cowen, L. E., Sanglard, D., Howard, S. J., Rogers, P. D., & Perlin, D. S. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019752 · Cited by 647
Regulatory circuitry governing fungal development, drug resistance, and disease.
Shapiro, R. S., Robbins, N., & Cowen, L. E. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00045-10 · Cited by 576
Metadata
- Authors
- Reinoso-Martín, C., Schüller, C., Schuetzer-Muehlbauer, M., & Kuchler, K.
- Affiliations
- Department of Medical Biochemistry, Division of Molecular Genetics, Max F. Perutz Laboratories, University and Biocenter of Vienna, A-1030 Vienna, Austria
- Max Perutz Labs (AT)
- Corresponding author
- Kuchler, Karl
- ORCID
- Kuchler, Karl
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2003-12
- Volume
- 2
- Issue
- 6
- Pages
- 1200-1210
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC326656
- OpenAlex
- W2106031809
- Cited by
- 193
- References
- 65
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 10 · 2021: 11 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 10 · 2016: 10 · 2015: 8 · 2014: 13 · 2013: 7 · 2012: 7
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Oesterreichische Nationalbank
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- caspofungin, echinocandins, antifungal drug tolerance, Saccharomyces cerevisiae, protein kinase C signaling, cell integrity pathway, mitogen-activated protein kinase, FKS1, cell wall biosynthesis, stress signaling, genome-wide gene expression
- MeSH terms
- Caspofungin, Antifungal Agents, Cell Extracts, Cell Survival, Cells, Cultured, DNA-Binding Proteins, Drug Tolerance, Enzyme Activation, Fungal Proteins, Genes, Fungal, Kinetics, Models, Biological, Peptides, Peptides, Cyclic, Phosphorylation, Protein Kinase C, Repressor Proteins, RNA, Messenger, Saccharomyces cerevisiae, Signal Transduction, Down-Regulation, Gene Expression, Oligonucleotide Array Sequence Analysis, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Saccharomyces cerevisiae Proteins, Echinocandins, Lipopeptides
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
