Evidence map›Paper›PMID 41584340›Full record

ArticleActa pharmaceutica Sinica. B2026

Radiation-induced nuclear translocation of NPRL2 hijacks E3 ubiquitin ligases to enhance DNA repair

Xuecen Wang, Yuxuan Zhao, Xingli Yang, Tingyu Liu, Weilin Zhou, Shaoqing Niu, Meng Jin, Yong Chen, Ran-Yi Liu, Yong Bao and 1 more

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In one paragraph

Article in Acta pharmaceutica Sinica. B, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

11 authors.

Xuecen WangDepartment of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Yuxuan ZhaoState Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, China.
Xingli YangDepartment of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Tingyu LiuState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Weilin ZhouState Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, China.
Shaoqing NiuDepartment of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Meng JinDepartment of Radiation Oncology and Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China.
Yong ChenDepartment of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Ran-Yi LiuState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Yong BaoDepartment of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Xin YueState Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Radiotherapy resistance remains a major clinical challenge in colorectal cancer (CRC) treatment. Our study reveals that the regulation of nuclear E3 ubiquitin ligase maintains K48-ubiquitin levels that correlate with CRC radiotherapy sensitivity. We identify NPRL2 as the central mediator of this process. Following radiation, NPRL2 rapidly translocates to the nucleus, where it directly binds to the catalytic domains of key E3 ubiquitin ligases, including HERC2 and RNF8, and functionally inactivates them. This NPRL2-mediated inhibition of E3 ligase activity prevents the degradation of critical DNA repair proteins. Importantly, clinical analyses demonstrate that nuclear NPRL2 plays a role in sustaining radioresistance. Mechanistic investigations reveal that radiation-induced AMPK activation initiates this process by phosphorylating WDR24, which promotes NPRL2 dissociation from the GATOR1 complex and facilitates its nuclear translocation. Therapeutic targeting through AMPK inhibition effectively blocks NPRL2 nuclear accumulation, leading to impaired DNA damage repair and significant radiosensitization of CRC cells in both

Indexed as

AMPK/WDR24 axisCRC radioresistanceDNA repairE3 ubiquitin ligasesNPRL2Nuclear translocationRadiation inductionTherapeutic target

Identifiers

PMID41584340
PMCPMC12828144

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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.