PXD063356-1

PXD063356 is an original dataset announced via ProteomeXchange.

Title	In Vivo Metabolic Labeling with an Isoprenoid Probe Reveals APOE Allele-specific Differences in the Prenylome
Description	Prenylation is a ubiquitous process in eukaryotes consisting of the irreversible post-translational modification of proteins through the attachment of a lipophilic isoprenoid moiety to a cysteine residue near their C-terminus. Due to the important functional roles of prenylated proteins, their participation and/or dysregulation have been linked to numerous diseases, including ALS, progeria, cancer and Alzheimer’s disease (AD). In humans, the APOE4 variant is the greatest known genetic risk factor for late-onset sporadic AD with carriers of two E4 alleles having up to 15 times the risk of developing AD. To begin to unravel the potential relationship between protein prenylation, AD and APOE variants, it is necessary to study whether different APOE genotypes affect protein prenylation systemically. In the work described here, methodology for metabolic labeling of prenylated proteins in living mice was first developed. It was then applied to humanized mouse strains that carry human APOE3 or APOE4 alleles. Prenylomic profiling revealed that a number of prenylated proteins were present at higher levels in animals harboring the APOE4 gene compared with those with the APOE3 allele, especially in the liver – a major APOE-producing organ. Importantly, some of these proteins have links to AD neuropathology.
HostingRepository	PRIDE
AnnounceDate	2025-10-27
AnnouncementXML	Submission_2025-10-26_17:23:21.806.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexandru Mihai Petre
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	farnesylated residue; TMT6plex-126 reporter+balance reagent acylated residue; biotinylated residue; geranylgeranylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-26 08:04:09	ID requested
⏵ 1	2025-10-26 17:23:22	announced

Petre AM, Thieschafer JS, Palsuledesai C, Cornille K, Chang A, Li L, Distefano MD, Metabolic Labeling with an Isoprenoid Probe Reveals APOE Allele-Specific Differences in the Prenylome. ACS Chem Biol, 20(8):1951-1961(2025) [pubmed]

10.1021/acschembio.5c00320;

submitter keyword: prenylation,APOE3, liver, kidney, transgenic mice, APOE4

Mark D. Distefano
contact affiliation	University of Minnesota
contact email	diste001@umn.edu
lab head
Alexandru Mihai Petre
contact affiliation	University of Minnesota
contact email	petre096@umn.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063356
     1. Label: PRIDE project
     2. Name: In Vivo Metabolic Labeling with an Isoprenoid Probe Reveals APOE Allele-specific Differences in the Prenylome