Evidence map›Paper›PMID 42323478›Full record

ArticleOncogene2026

SPOP-mediated nuclear ubiquitination degradation of p62/SQSTM1 contributes to HR repair.

Xiaojuan Yang, Ying Zhou, Qing Huang, Lingli Wang, Su Zhang, Xuyang Yang, Lei Qiu, Yang Meng, Hong Wu, Bo Zhang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 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

13 authors.

Xiaojuan YangDivision of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. y3532388972@163.com.ORCID http://orcid.org/0009-0006-9430-6482
Ying ZhouDivision of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Qing HuangLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, Department of Gastrointestinal Surgery, Cancer Center and State Laboratory of Biotherapy, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Lingli WangLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, Department of Gastrointestinal Surgery, Cancer Center and State Laboratory of Biotherapy, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Su ZhangLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, Department of Gastrointestinal Surgery, Cancer Center and State Laboratory of Biotherapy, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Xuyang YangLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, Department of Gastrointestinal Surgery, Cancer Center and State Laboratory of Biotherapy, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Lei QiuLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, Department of Gastrointestinal Surgery, Cancer Center and State Laboratory of Biotherapy, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Yang MengLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, Department of Gastrointestinal Surgery, Cancer Center and State Laboratory of Biotherapy, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Hong WuLaboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0002-0885-4911
Bo ZhangLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, Department of Gastrointestinal Surgery, Cancer Center and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Kunlin XieLaboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. xiekun@scu.edu.cn.ORCID http://orcid.org/0009-0007-6609-0511
Junhong HanLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, Department of Gastrointestinal Surgery, Cancer Center and State Laboratory of Biotherapy, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. hjunhong@scu.edu.cn.ORCID http://orcid.org/0000-0002-3371-8698
Qing ZhuDivision of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. newzhuqing1972@163.com.ORCID http://orcid.org/0000-0003-2182-5709

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82073481
6 · The paper itself

Abstract

Dysregulation of Speckle-type POZ protein (SPOP) and cargo receptor p62/SQSTM1 impairs homologous recombination (HR)-mediated DNA repair by destabilizing RAD51 and FLNA, yet their mechanistic interplay in genomic stability and oncogenesis remains unclear. In this study, we found that the interaction between SPOP and p62/SQSTM1 is obviously enhanced in nucleus in response to DNA damage. Moreover, the nuclear ubiquitination of p62/SQSTM1 at lysine 7 by SPOP led to its degradation, resulting in upregulation of RAD51 and FLNA, RAD51 foci formation, and HR efficiency. In addition, patients-derived p62/SQSTM1 mutations in SPOP-binding consensus (SBC) motif (S276Y/S277G/S277I) increased radiotherapy sensitivity in vitro and in vivo, which attributes to HR deficiency caused by increased degradation of RAD51 and FLNA proteins, and decreased RAD51 and γ-H2AX foci formation. Our finding provides insight into the regulation of HR by SPOP and p62/SQSTM1, and disrupting the interaction between SPOP, p62/SQSTM1 and nuclear ubiquitination may be a potential approach for overcoming radiotherapy resistance in cancer.

Indexed as

Cell NucleusNuclear ProteinsRecombinational DNA RepairRepressor ProteinsSequestosome-1 ProteinAnimalsCell Line, TumorDNA DamageHumansMiceRad51 RecombinaseUbiquitinationNuclear ProteinsRad51 RecombinaseRepressor ProteinsSequestosome-1 ProteinSPOP protein, humanSQSTM1 protein, human

Identifiers

PMID42323478
PMCPMC13384900

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.