Evidence map›Paper›PMID 40742808›Full record

ArticleCell reports2025

PFKFB3 activates CAD to enhance de novo pyrimidine synthesis for cell growth.

Qingen Da, Yongfeng Cai, Qian Ma, Qiuhua Yang, Yapeng Cao, Yaqi Zhou, Dingwei Zhao, Zhiping Liu, Jiean Xu, Junming Quan and 15 more

Erratum issuedAbstract read
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In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Qingen DaState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Hospital, Peking University Shenzhen Graduate School, Shenzhen 518055, China; Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Yongfeng CaiState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Hospital, Peking University Shenzhen Graduate School, Shenzhen 518055, China; Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Departments of Ophthalmology, Medicine, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Qian MaVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Departments of Ophthalmology, Medicine, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Qiuhua YangVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Yapeng CaoVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Yaqi ZhouVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Dingwei ZhaoVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Departments of Ophthalmology, Medicine, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Zhiping LiuVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Jiean XuVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Junming QuanState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Hospital, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Liang ZhangDepartment of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon 999077, Hong Kong, China.
Rui WangDepartment of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon 999077, Hong Kong, China.
Xuejun JiangInstitute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Xiao LiuInstitute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Kunfu OuyangState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Hospital, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Zhen HanState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Hospital, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Jikui LiuState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Hospital, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Tao WangState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Hospital, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Chunxiang ZhangDepartment of Cardiology, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, China.
Neal L WeintraubVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
David J R FultonVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Jun ZhaoCleveland Clinic, Florida Research & Innovation Center (FRIC), Port Saint Lucie, FL 34987, USA.
Mei HongState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Hospital, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Zigang LiState Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Hospital, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Yuqing HuoVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Departments of Ophthalmology, Medicine, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: yuqing.huo@bcm.edu.

Funding

American Heart Association-American Stroke Association 968801
6 · The paper itself

Abstract

Aerobic glycolysis, 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. Research on the direct interactions between glycolysis and other metabolic pathways is an emerging field that has garnered significant interest. 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 cell proliferation. Thus, the glycolytic activator PFKFB3 bridges glycolysis with pyrimidine synthesis, unites both glucose metabolism and nucleic acid metabolism, and contributes to cell proliferation under pathological conditions.

Indexed as

Aspartate CarbamoyltransferaseDihydroorotasePhosphofructokinase-2PyrimidinesAnimalsCarbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)Cell ProliferationGlycolysisHumansMicePhosphorylationAspartate CarbamoyltransferaseCarbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)DihydroorotasePFKFB3 protein, humanPhosphofructokinase-2pyrimidinePyrimidinesCADCP: MetabolismCP: Molecular biologyde novo pyrimidine synthesisglycolysiskinase activityPFKFB3Warburg effect

Identifiers

PMID40742808
PMCPMC12648754

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.