PXD002727 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteomic profiling of Cryptococcus neoformans |
Description | The opportunistic fungal pathogen Cryptococcus neoformans causes life-threatening meningitis in immunocompromised individuals. The expression of virulence factors including capsule and melanin is in part regulated by the cyclic-AMP/Protein Kinase A (PKA) signal transduction pathway. In this study, we investogated the influence of PKA on the composition of the intracellular proteome to obatin a comprehensive understanding of the regulation that underpins virulence. Through quantitative proteomics, enrichment and bioinformatic analyses, and an interactome study, we discovered a conserved pattern of PKA regulation for proteins associated with translation, the proteasome, metabolism, amino acid biosynthesis, and virulence-related functions. PKA regulation of the ubiquitin-proteasome pathway in C. neoformans showed a striking parallel with connections between PKA and protein degradation in chronic neurodegenerative disorders and other human diseases. Further investigation using the proteasome inhibitor bortezomib revealed an impact on capsule production and fungal growth. These results prompted additional studies of the antifungal activity of bortezomib in the context of cAMP signlaing and in combination with fluconazole. Taken together, the data suggest a model whereby PKA activation causes a shift in proteostasis and the function of the endoplasmic reticulum to support the synthesis and export of capsule polysaccharide. Overall, this study revealed a remarkably broad and conserved influence of the cAMP/PKA pathway on the proteome, and identified proteostasis as a potential therapeutic target for the treatment of cryptococcosis. |
HostingRepository | PRIDE |
AnnounceDate | 2016-01-18 |
AnnouncementXML | Submission_2016-01-18_08:58:53.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jennifer Geddes-McAlister |
SpeciesList | scientific name: Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 / CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii); NCBI TaxID: 235443; |
ModificationList | monohydroxylated residue; 2x(13)C: 6x(2)H labeled dimethylated L-arginine |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2015-08-14 06:14:36 | ID requested | |
⏵ 1 | 2016-01-18 08:58:54 | announced | |
Publication List
Geddes JM, Caza M, Croll D, Stoynov N, Foster LJ, Kronstad JW, Analysis of the Protein Kinase A-Regulated Proteome of Cryptococcus neoformans Identifies a Role for the Ubiquitin-Proteasome Pathway in Capsule Formation. mBio, 7(1):e01862-15(2016) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Proteomics, fungal pathogenesis, cAMP/PKA pathway, virulence |
Contact List
James W. Kronstad |
contact affiliation | Michael Smith Laboratories, University of British Columbia |
contact email | kronstad@msl.ubc.ca |
lab head | |
Jennifer Geddes-McAlister |
contact affiliation | Max Planck Institute for Biochemistry |
contact email | geddes@biochem.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD002727
- Label: PRIDE project
- Name: Proteomic profiling of Cryptococcus neoformans