Evidence map›Paper›PMID 40695785›Full record

ArticleNature communications2025

PFKM phosphorylates histone H3 and promotes mitotic progression by sensing the levels of citrate.

Pianpian Lin, Yijun Qi, Huiying Chu, Hongyu Wu, Yajuan Zhang, Xiaolan Huang, Chen Li, Xiaoyan Xu, Hong Gao, Rong Zeng and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

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

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Pianpian Lin *Key Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China.
Yijun Qi *Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
Huiying Chu *Interdisciplinary Research Center for Biology and Chemistry, Liaoning Normal University, Dalian, China.ORCID http://orcid.org/0000-0002-0018-6189
Hongyu WuKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China.
Yajuan ZhangKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China.
Xiaolan HuangKey Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
Chen LiCenter for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-6367-0998
Xiaoyan XuMass Spectrometry & Metabolomics Core Facility, Biomedical Research Core Facilities, Westlake University, Hangzhou, China.
Hong GaoKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China.
Rong ZengKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China.
Guohui LiInterdisciplinary Research Center for Biology and Chemistry, Liaoning Normal University, Dalian, China. ghli@dicp.ac.cn.ORCID http://orcid.org/0000-0001-8223-705X
Weiwei YangKey Laboratory of Multi-cell Systems, Shanghai Key Laboratory of Molecular Andrology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China. wyang@sibcb.ac.cn.ORCID http://orcid.org/0000-0002-1661-9137

Funding

National Natural Science Foundation of China (National Science Foundation of China) 92357301, 92253305, and 32025013Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 24J12800600
6 · The paper itself

Abstract

Emerging evidence indicates that metabolic signals-including nutrient availability, biosynthetic intermediates, and energy balance-are linked to cell cycle progression. However, how these signals are sensed by the cell cycle machinery remains unclear. Citrate, a key intermediate in the TCA cycle, peaks during mitosis (M phase) and is detected by the glycolytic enzyme ATP-dependent 6-phosphofructokinase 1 muscle isoform (PFKM), accelerating mitotic progression. Mechanistically, citrate binds PFKM, disrupting its tetrameric structure into dimers. Dimeric PFKM interacts with nucleosomes and phosphorylates histone H3 at serine 10 (H3S10), functioning as a protein kinase to promote mitosis and cell proliferation. Structural simulations reveal that PFKM binds nucleosomes optimally when H3S10 aligns with its catalytic site. Disrupting citrate-PFKM or PFKM-H3 interactions reduces H3S10 phosphorylation, delays mitosis, and suppresses tumor growth and T-cell proliferation. Our findings demonstrate that PFKM acts as a citrate sensor, coupling metabolic signals to cell cycle regulation.

Indexed as

Citric AcidHistonesMitosisAnimalsCell ProliferationHumansMiceNucleosomesPhosphorylationCitric AcidHistonesNucleosomes

Identifiers

PMID40695785
PMCPMC12283967

What OpenQuestion holds

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Registered trials

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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.