PXD048755-1

PXD048755 is an original dataset announced via ProteomeXchange.

Title	PFKFB3 activates CAD to enhance de novo pyrimidine synthesis for cell growth
Description	Aerobic glycolysis, which is also termed the Warburg effect, is one of the aberrant metabolic pathways in highly proliferating cells. Glycolysis provides glycolytic metabolites to support the generation of biomass, such as nucleotides, amino acids, and lipids. To date, no studies have explored interrelationships between glycolysis and other metabolic pathways. Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) activates glycolysis by synthesizing fructose-2,6-bisphosphate (F2,6BP), which allosterically activates the rate-limiting enzyme 6-phosphofructo-1-kinase (PFK-1). In this study, we found that PFKFB3 directly interacts with and regulates the phosphorylation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), the enzyme catalyzing the first three steps of de novo pyrimidine synthesis. PFKFB3 inactivation reduced de novo pyrimidine synthesis, RNA and DNA production, and the growth of cancer and proliferative cells. Thus, the glycolytic activator PFKFB3 bridges glycolysis with pyrimidine synthesis, unites both glucose metabolism and nucleic acid metabolism, and contributes to cell proliferation under both physiological and pathological conditions.
HostingRepository	PRIDE
AnnounceDate	2025-06-16
AnnouncementXML	Submission_2025-06-16_09:49:07.194.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Qingen Da
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-22 03:08:12	ID requested
⏵ 1	2025-06-16 09:49:07	announced

Dataset with its publication pending

ProteomeXchange project tag: Cancer (B/D-HPP), Cardiovascular (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Human, Co-IP, Phosphoproteomic

Yuqing Huo
contact affiliation	Augusta University Medical College of Georgia
contact email	YHUO@augusta.edu
lab head
Qingen Da
contact affiliation	Peking University Shenzhen Hospital
contact email	daqen@mail3.sysu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048755
     1. Label: PRIDE project
     2. Name: PFKFB3 activates CAD to enhance de novo pyrimidine synthesis for cell growth