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PXD041329

PXD041329 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism
DescriptionAccumulation 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_09:09:38.912.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRalf Pflanz
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-04-04 08:36:39ID requested
12023-10-24 12:29:50announced
22023-11-14 09:09:39announced2023-11-14: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: Prox1,SUMOylation, Cholesterol, Liver, Bile acids
Contact List
Stephan Herzig
contact affiliation1 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 emailstephan.herzig@helmholtz-munich.de
lab head
Ralf Pflanz
contact affiliationMPInat AG16080
contact emailrpflanz@mpinat.mpg.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
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