PXD041329-1

PXD041329 is an original dataset announced via ProteomeXchange.

Title	Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism
Description	Accumulation of excess nutrients hampers proper liver function and is linked to non-alcoholic fatty liver disease (NAFLD) in obesity. However, the signals responsible for an impaired adaptation of hepatocytes to obesogenic dietary cues remain still largely unknown. Post-translational modification by the Small Ubiquitin-like Modifier (SUMO), allows for adynamic regulation of numerous processes including transcriptional reprograming. We demonstrate that specific SUMOylation of transcription factor Prox1 represents a nutrient-sensitive determinant of hepatic fasting metabolism. Prox1 was highly SUMOylated on lysine 556 in the liver of ad libitum and re-fed mice, while this modification was abolished upon fasting. In the context of diet-induced obesity, Prox1 SUMOylation became less sensitive to fasting cues. The hepatocyte-selective knock-in of a SUMOylation-deficient Prox1 mutant into mice fed a high-fat/high-fructose diet led to a reduction of systemic cholesterol levels, associated with the induction of liver bile acid detoxifying pathways during fasting. The generation of tools to maintain the nutrient-sensitive SUMO-switch on Prox1 may thus contribute to the development of “fasting-based” approaches for the preservation of metabolic health.
HostingRepository	PRIDE
AnnounceDate	2023-10-24
AnnouncementXML	Submission_2023-10-24_12:29:49.849.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	RalfPflanz
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-04 08:36:39	ID requested
⏵ 1	2023-10-24 12:29:50	announced
2	2023-11-14 09:09:39	announced	2023-11-14: Updated project metadata.

Alfaro AJ, Dittner C, Becker J, Loft A, Mhamane A, Maida A, Georgiadi A, Tsokanos FF, Klepac K, Molocea CE, El-Merahbi R, Motzler K, Geppert J, Karikari RA, Szendr, ö, di J, Feuchtinger A, Hofmann S, Karaca S, Urlaub H, Berriel Diaz M, Melchior F, Herzig S, Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism. EMBO Rep, 24(10):e55981(2023) [pubmed]

submitter keyword: Prox1,SUMOylation, Cholesterol, Liver, Bile acids

StephanHerzig
contact affiliation	1 Institute for Diabetes and Cancer, Helmholtz Munich, Neuherberg, Germany 2 Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany 3 German Center for Diabetes Research (DZD), and German Center for Cardiovascular Disease (DZHK), Neuherberg, Germany 4 Chair Molecular Metabolic Control, Technical University Munich, Germany
contact email	stephan.herzig@helmholtz-munich.de
lab head
RalfPflanz
contact affiliation	MPInat AG16080
contact email	rpflanz@mpinat.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD041329

PRIDE project URI

• PRIDE
  1. PXD041329
     1. Label: PRIDE project
     2. Name: Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism