Evidence map›Paper›PMID 40339118›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

VCP's nuclear journey: Initiated by interacting with KPNB1 to repair DNA damage.

Zhichao Xing, Xiaoying Cai, Ting He, Peiheng Li, Jun He, Yuxuan Qiu, Na Li, Li Mi, Ruixi Li, Jingqiang Zhu and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 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. Review
  2. TRMT6-directed mNPJ precision oncology · 2026
    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

14 authors.

Zhichao Xing *Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.ORCID 0000-0003-0638-4597
Xiaoying Cai *Department of Biotherapy, Cancer Center and State Key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.ORCID 0000-0002-9650-0063
Ting He *Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.ORCID 0009-0006-0434-2122
Peiheng Li *Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
Jun HeLaboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610041, China.
Yuxuan QiuDepartment of Ultrasound, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310030, China.ORCID 0000-0002-5467-6466
Na LiDepartment of Biotherapy, Cancer Center and State Key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Li MiDivision of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.ORCID 0000-0002-8007-6958
Ruixi LiDivision of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
Jingqiang ZhuDivision of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhihui LiDivision of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
Anping SuDivision of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
Haoyu YeDepartment of Biotherapy, Cancer Center and State Key laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Wenshuang WuDivision of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.ORCID 0000-0002-1210-4865

Funding

SCU | West China Hospital, Sichuan University (WCH) CGZH19010Sichuan University (SCU) 2018SCUH0067SPDST | Sichuan Provincial Science and Technology Support Program (Science and Technology Project of Sichuan) 2024NSFSC1871SPDST | Sichuan Provincial Science and Technology Support Program (Science and Technology Project of Sichuan) 2024YFHZ0185
6 · The paper itself

Abstract

DNA damage repair (DDR) is essential for cancer cell survival and treatment resistance, making it a critical target for tumor therapy. The eukaryotic AAA+ adenosine triphosphatase valosin-containing protein (VCP), which is transported from the cytoplasm into the nucleus, plays a critical role in the DDR process. However, the nuclear translocation and molecular mechanism of VCP for DDR remain elusive. Here, we define VCP as a KPNB1 interacting protein through a combination of chemical and immunoprecipitation mass spectrometry approaches. Further biochemical studies elucidate that KPNB1 directly transports VCP into the nucleus. We also identify withaferin A (WA) as a small molecule that can retard VCP nuclear localization via covalent binding to CYS 158 of KPNB1. Further studies verify WA as an effective antitumor drug candidate via blocking VCP nuclear localization to impact on the DDR pathway in vivo. Our findings underly the unclear VCP's role in DDR in a KPNB1-dependent manner and provide an important theoretical basis for developing small-molecule inhibitors targeting this process.

Indexed as

Adenosine Triphosphatasesbeta KaryopherinsCell Cycle ProteinsCell NucleusDNA DamageDNA RepairValosin Containing ProteinActive Transport, Cell NucleusAnimalsCell Line, TumorHumansMiceProtein BindingWithanolidesAdenosine Triphosphatasesbeta KaryopherinsCell Cycle ProteinsValosin Containing ProteinVCP protein, humanWithanolidesDNA damage repairKPNB1nuclear translocationVCPwithaferin A

Identifiers

PMID40339118
PMCPMC12088430

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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.