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PXD043435

PXD043435 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHijacking of Nucleotide Biosynthesis and Deamidation-mediated Glycolysis by an Oncogenic Herpesvirus
DescriptionKaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma (KS) and multiple types of B cellmalignancies. Emerging evidence demonstrates that KSHV reprograms host-cell central carbon metabolic pathways, which contributesto viral persistence and tumorigenesis. However, the mechanisms underlying KSHV-mediated metabolic reprogramming remain poorlyunderstood. Carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) is a key enzyme of the denovo pyrimidine synthesis, and was recently identified to deamidate the NF-κB subunit RelA to promote aerobic glycolysis and cellproliferation. Here we report that KSHV infection exploits CAD for nucleotide synthesis and glycolysis. Mechanistically, KSHV vCyclin binds to and hijacks cyclin-dependent kinase CDK6 to phosphorylate Ser-1900 on CAD, thereby activating CAD-mediatedpyrimidine synthesis and RelA-deamidation-mediated glycolytic reprogramming. Correspondingly, genetic depletion orpharmacological inhibition of CDK6 and CAD potently impeded KSHV lytic replication and thwarted tumorigenesis of primaryeffusion lymphoma (PEL) cells in vitro and in vivo. Altogether, our work defines a viral metabolic reprogramming mechanismunderpinning KSHV oncogenesis, which may spur the development of new strategies to treat KSHV-associated malignancies and otherdiseases.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:31:00.494.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJun Zhao
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-06-30 08:13:05ID requested
12024-02-16 11:50:48announced
22024-10-22 06:31:00announced2024-10-22: Updated project metadata.
Publication List
10.1038/S41467-024-45852-5;
Keyword List
submitter keyword: LC-MSMS
Contact List
Jun Zhao
contact affiliationCleveland Clinic Florida Research and Innovation Center
contact emailzhaoj6@ccf.org
lab head
Jun Zhao
contact affiliationCleveland Clinic Florida Research and Innovation Center
contact emailzhaoj6@ccf.org
dataset submitter
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Dataset FTP location
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