Evidence map›Paper›PMID 42844274›Full record

ArticleNature communications2026

CBX4 stabilizes NEUROD1 through SUMO-ubiquitin crosstalk to delay β-cell senescence.

Linming Su, Yan Liu, Qianxing Hu, Hongjin Chen, Yimeng Qin, Chenying Xu, Kun Gao, Yuncai Zhou, Yue Yang, Jianxing Liu and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

17 authors.

Linming Su *State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Yan Liu *State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Qianxing Hu *State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Hongjin ChenState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Yimeng QinState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Chenying XuState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Kun GaoState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Yuncai ZhouDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.ORCID 0000-0002-9731-203X
Yue YangState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Jianxing LiuState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Yi PanState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.ORCID 0000-0002-5742-3202
Yanfeng ZhangState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Fengjiao HuoInstitute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Xiaohang ZhouKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
Hailiang LiuInstitute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. hailiang_1111@tongji.edu.cn.ORCID 0000-0002-5521-3746
Liang JinState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. ljstemcell@cpu.edu.cn.ORCID 0000-0002-4995-3553
Fangfang ZhangState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. zhangff@cpu.edu.cn.ORCID 0000-0002-1954-4345

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82373925,82070801
6 · The paper itself

Abstract

Aging-associated β-cell senescence is a key driver of type 2 diabetes mellitus (T2DM). However, its associated molecular mechanisms remain poorly explored. This study identifies Chromobox 4 (CBX4), a Polycomb group protein with SUMO E3 ligase activity, as an essential regulator of β-cell aging and function. The results show that CBX4 expression progressively downregulates in both aged and diabetic pancreatic islets. Targeted deletion of Cbx4 in β-cell accelerates cellular senescence, impairs glucose tolerance, and compromises mitochondrial function. CBX4 interacts directly with the transcription factor NEUROD1 via its SUMO-interacting motif 1 (SIM1). CBX4 promotes SUMOylation of NEUROD1 at lysine 38 and drives its assembly into nuclear condensates via phase separation. These processes collectively antagonize NEDD4-mediated ubiquitination at the same site, stabilizing NEUROD1. The preserved NEUROD1 enhances Ins2 transcription and suppresses Camk2n1 expression, thus activating CaMKII signaling, promoting calcium influx, and maintaining mitochondrial bioenergetics. Furthermore, the study identifies STAT5A as a transcriptional regulator upstream of Cbx4. These findings reveal a STAT5A-CBX4-NEUROD1 signaling axis associated with β-cell aging in T2DM and suggest CBX4 as a promising therapeutic target to maintain β-cell function in metabolic disorders.

Indexed as

Basic Helix-Loop-Helix ProteinsCellular SenescenceInsulin-Secreting CellsPolycomb-Group ProteinsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Diabetes Mellitus, Type 2HumansLigasesMiceMitochondriaSignal TransductionSumoylationUbiquitinUbiquitinationBasic Helix-Loop-Helix ProteinsCalcium-Calmodulin-Dependent Protein Kinase Type 2CBX4 protein, humanLigasesNeurod1 protein, mousePolycomb-Group ProteinsUbiquitin

Identifiers

PMID42844274
PMCPMC13645805

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.