PXD043435

PXD043435 is an original dataset announced via ProteomeXchange.

Title	Hijacking of Nucleotide Biosynthesis and Deamidation-mediated Glycolysis by an Oncogenic Herpesvirus
Description	Kaposi’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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:31:00.494.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jun Zhao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-30 08:13:05	ID requested
1	2024-02-16 11:50:48	announced
⏵ 2	2024-10-22 06:31:00	announced	2024-10-22: Updated project metadata.

10.1038/S41467-024-45852-5;

submitter keyword: LC-MSMS

Jun Zhao
contact affiliation	Cleveland Clinic Florida Research and Innovation Center
contact email	zhaoj6@ccf.org
lab head
Jun Zhao
contact affiliation	Cleveland Clinic Florida Research and Innovation Center
contact email	zhaoj6@ccf.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043435
     1. Label: PRIDE project
     2. Name: Hijacking of Nucleotide Biosynthesis and Deamidation-mediated Glycolysis by an Oncogenic Herpesvirus