Evidence map›Paper›PMID 30874560›Full record

ArticleNature communications2019

The deubiquitylating enzyme USP15 regulates homologous recombination repair and cancer cell response to PARP inhibitors.

Yihan Peng, Qingchao Liao, Wei Tan, Changmin Peng, Zhaohua Hu, Yali Chen, Zhuqing Li, Jing Li, Bei Zhen, Wenge Zhu and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% of its field
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

76 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

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  19. The CYLD-PARP1 feedback loop regulates DNA damage repair and chemosensitivity in breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Review

16 more citing papers are in PubMed but not listed here.

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 at 6 institutions in 2 countries.

Yihan PengState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, 102206, China.
Qingchao LiaoState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, 102206, China.
Wei TanDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC, 20037, USA.
Changmin PengCancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Zhaohua HuState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, 102206, China.
Yali ChenState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, 102206, China.
Zhuqing LiDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC, 20037, USA.
Jing LiDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC, 20037, USA.ORCID http://orcid.org/0000-0002-0079-693X
Bei ZhenState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, 102206, China.
Wenge ZhuDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC, 20037, USA.
Xiangpan LiCancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Yi YaoCancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Qibin SongCancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Chengsheng LiuAesthetic Surgery, Jingmei Cosmetic Surgery Clinic, Beijing, 100124, China.
Xiangdong QiDepartment of Plastic Surgery, General Hospital of Southern Theater Command, PLA, Liuhua Road 111, Guangzhou, 510010, China. create_beauty@hotmail.com.
Fuchu HeState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, 102206, China. hefc@nic.bmi.ac.cn.
Huadong PeiState Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, 102206, China. peihuadong@hotmail.com.
George Washington University · USBeijing Proteome Research Center · CNWuhan University · CNGeneral Hospital of Guangzhou Military Command · CNGeorgetown University · USTianjin University of Science and Technology · CN

Funding

The Role of And-1 in DNA Damage ResponseR01CA177898 · NCI · GEORGE WASHINGTON UNIVERSITY · PI ZHU, WENGE · 2014 to 2018
$1.6M
The Regulation of Cisplatin resistance in ovarian cancerR01CA184717 · NCI · GEORGE WASHINGTON UNIVERSITY · PI ZHU, WENGE · 2014 to 2018
$1.6M
NCI NIH HHS R01 CA177898NCI NIH HHS R01 CA184717
6 · The paper itself

Abstract

Poly-(ADP-ribose) polymerase inhibitors (PARPi) selectively kill breast and ovarian cancers with defects in homologous recombination (HR) caused by BRCA1/2 mutations. There is also clinical evidence for the utility of PARPi in breast and ovarian cancers without BRCA mutations, but the underlying mechanism is not clear. Here, we report that the deubiquitylating enzyme USP15 affects cancer cell response to PARPi by regulating HR. Mechanistically, USP15 is recruited to DNA double-strand breaks (DSBs) by MDC1, which requires the FHA domain of MDC1 and phosphorylated Ser678 of USP15. Subsequently, USP15 deubiquitinates BARD1 BRCT domain, and promotes BARD1-HP1γ interaction, resulting in BRCA1/BARD1 retention at DSBs. USP15 knockout mice exhibit genomic instability in vivo. Furthermore, cancer-associated USP15 mutations, with decreased USP15-BARD1 interaction, increases PARP inhibitor sensitivity in cancer cells. Thus, our results identify a novel regulator of HR, which is a potential biomarker for therapeutic treatment using PARP inhibitors in cancers.

Indexed as

Recombinational DNA RepairAdaptor Proteins, Signal TransducingAnimalsCell Cycle ProteinsDNA Breaks, Double-StrandedDrug Resistance, NeoplasmHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsKaplan-Meier EstimateMCF-7 CellsMiceMice, Inbred C57BLMice, KnockoutMutationNeoplasmsAdaptor Proteins, Signal TransducingBARD1 protein, humanBard1 protein, mouseCell Cycle ProteinsIntracellular Signaling Peptides and ProteinsMDC1 protein, humanMDC1 protein, mouseNuclear ProteinsPoly(ADP-ribose) Polymerase InhibitorsRNA, Small InterferingTrans-ActivatorsTumor Suppressor ProteinsUbiquitin-Protein LigasesUbiquitin-Specific ProteasesUSP15 protein, humanUsp15 protein, mouse

Identifiers

PMID30874560
PMCPMC6420636
OpenAlexW2920931417

What OpenQuestion holds

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LicenceCC BY
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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.