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PXD002150

PXD002150 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAn integrated systems biology approach reveals positive and negative effects of suberoylanilide hydroxamic acid (SAHA) on HIV reactivation from latency
DescriptionSuberoylanilide hydroxamic acid (SAHA) has been assessed in clinical trials as part of a “shock and kill” strategy to cure HIV-infected patients. While it was effective at inducing expression of HIV RNA "shock" , treatment with SAHA did not result in the reduction of reservoir size "kill". We therefore utilized a systems biology approach to dissect the mechanisms of action of SAHA that may explain its limited success in “shock and kill” strategies. CD4+ T cells from HIV seronegative donors were treated with 1 uM SAHA or its solvent dimethyl sulfoxide for 24 hours. Differential protein expression and post-translational modification was measured with two-dimensional liquid chromatography - tandem mass spectrometry iTRAQ proteomics. Gene expression changes were assessed by Illumina microarrays. Using limma package in the R computing environment, we identified 185 proteins, 18 phosphorylated forms, 4 acetylated forms and 2,982 genes, whose expression was modulated by SAHA. A protein interaction network integrating these 4 data types identified the transcriptional regulator HMGA1 to be upregulated by SAHA at the transcript, protein and acetylated protein levels. HMGA1 has been shown to repress HIV transcription, which is not optimal with respect to a shock and kill strategy. Further functional category assessment of proteins and genes modulated by SAHA identified gene ontology terms related to NFB signaling, protein folding and autophagy, which are all relevant to HIV reactivation. In summary, this study identified a number of host factors that may be therapeutically targeted to achieve more potent HIV reactivation in the “shock and kill” treatment, when using SAHA, either through modification of SAHA itself or through combination with other latency reversing agents. Finally, proteome profiling highlighted a number of potential adverse effects of SAHA, which transcriptome profiling alone would not have identified.
HostingRepositoryPRIDE
AnnounceDate2015-09-10
AnnouncementXMLSubmission_2015-09-10_07:58:28.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHarvey Johnston
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListdeamidated residue; monohydroxylated residue; iTRAQ8plex-116 reporter+balance reagent acylated residue; acetylated residue; phosphorylated residue; methylthiolated residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02015-05-07 01:06:20ID requested
12015-09-10 07:58:29announced
Publication List
White CH, Johnston HE, Moesker B, Manousopoulou A, Margolis DM, Richman DD, Spina CA, Garbis SD, Woelk CH, Beliakova-Bethell N, Mixed effects of suberoylanilide hydroxamic acid (SAHA) on the host transcriptome and proteome and their implications for HIV reactivation from latency. Antiviral Res, 123():78-85(2015) [pubmed]
Keyword List
curator keyword: Biomedical, Biological
submitter keyword: CD4 T-cells, Human, SAHA, HIV latency, suberoylanilide hydroxamic acid
Contact List
Spiros D. Garbis
contact affiliationSpiros D. Garbis, PhD Faculty of Medicine, Cancer Sciences and CES Units, Institute for Life Sciences, University of Southampton 3001, Life Sciences Building 85, Highfield Campus Southampton, SO17 1BJ, UK Tel: 0044 02380593483
contact emailS.D.Garbis@soton.ac.uk
lab head
Harvey Johnston
contact affiliationUniversity of Southampton
contact emailh.johnston@soton.ac.uk
dataset submitter
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Dataset FTP location
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