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PXD045988

PXD045988 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTankyrase1/2 inhibition reveals that PARylation is regulating aerobic activities in hepatocytes and HepG2 cells
DescriptionXAV-939 is an anti-oncogenic small molecule that potently inhibits tankyrase1/2 (TNKS1/2), thereby blocking protein poly ADP-ribosylation (PARylation) of pleiotropic protein targets. In the present study, XAV-939 was used to explore its potential for improving human-derived liver models in vitro. Epithelial-to-mesenchymal transitioning indeed seemed to be reduced in XAV-939 treated primary human hepatocytes and HepG2 cells, while nutritional homeostasis, mitochondrial function, and CYP450-mediated biotransformation capacities were enhanced. Subsequently, CRISPR/Cas9 was utilised to generate tankyrase1 and/or tankyrase2 knockout HepG2 cells, which elucidated PARylation as master regulator for aerobic-dependent respiration. Novel (in)direct TNKS1/2-mediated PARylation targets were identified, using targeted proteomics and MS-coupled anti-PAR co-immunoprecipitation. In conclusion, XAV-939 can be applied to improve state-of-the art hepatic models in vitro in terms of metabolism and aerobic respiration. This work sheds light on a new mechanistic framework by linking PARylation to respiration and metabolism, thereby broadening the current understanding that underlies these vital processes.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:51:14.293.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJustina Clarinda Wolters
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-10-09 05:20:00ID requested
12024-07-25 09:34:44announced
22024-10-22 06:51:14announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Human, DIA HRMS1, tankyrase, IP, parylation
Contact List
Dr. Justina
contact affiliationLaboratory of Paediatrics, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
contact emailj.c.wolters@umcg.nl
lab head
Justina Clarinda Wolters
contact affiliationUMCG
contact emailj.c.wolters@umcg.nl
dataset submitter
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Dataset FTP location
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PRIDE project URI
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