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PXD002727

PXD002727 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomic profiling of Cryptococcus neoformans
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2016-01-18
AnnouncementXMLSubmission_2016-01-18_08:58:53.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJennifer 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;
ModificationListmonohydroxylated residue; 2x(13)C: 6x(2)H labeled dimethylated L-arginine
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02015-08-14 06:14:36ID requested
12016-01-18 08:58:54announced
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 affiliationMichael Smith Laboratories, University of British Columbia
contact emailkronstad@msl.ubc.ca
lab head
Jennifer Geddes-McAlister
contact affiliationMax Planck Institute for Biochemistry
contact emailgeddes@biochem.mpg.de
dataset submitter
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