PXD045988

PXD045988 is an original dataset announced via ProteomeXchange.

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

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.

Dataset with its publication pending

submitter keyword: Human, DIA HRMS1, tankyrase, IP, parylation

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

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PRIDE project URI

• PRIDE
  1. PXD045988
     1. Label: PRIDE project
     2. Name: Tankyrase1/2 inhibition reveals that PARylation is regulating aerobic activities in hepatocytes and HepG2 cells