PXD045988 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Tankyrase1/2 inhibition reveals that PARylation is regulating aerobic activities in hepatocytes and HepG2 cells |
Description | XAV-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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:51:14.293.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Justina Clarinda Wolters |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-10-09 05:20:00 | ID requested | |
1 | 2024-07-25 09:34:44 | announced | |
⏵ 2 | 2024-10-22 06:51:14 | announced | 2024-10-22: 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 affiliation | Laboratory of Paediatrics, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands |
contact email | j.c.wolters@umcg.nl |
lab head | |
Justina Clarinda Wolters |
contact affiliation | UMCG |
contact email | j.c.wolters@umcg.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD045988
- Label: PRIDE project
- Name: Tankyrase1/2 inhibition reveals that PARylation is regulating aerobic activities in hepatocytes and HepG2 cells