Evidence map›Paper›PMID 24556694›Full record

ArticleCell death & disease2014

A small-molecule inhibitor of UBE2N induces neuroblastoma cell death via activation of p53 and JNK pathways.

J Cheng, Y-H Fan, X Xu, H Zhang, J Dou, Y Tang, X Zhong, Y Rojas, Y Yu, Y Zhao and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
6.6field-weighted citation impact, top 3% 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, 103 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Covalent inhibition ofiScience · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Suppressing UBE2N ameliorates Alzheimer's disease pathology through the clearance of amyloid beta.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  17. Article
  18. Article
  19. Article
  20. Article

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 4 institutions in 2 countries.

J Cheng1] Department of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China [2] Department of Pediatrics, Texas Children's Cancer Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Y-H FanDepartment of Pediatrics, Texas Children's Cancer Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
X XuDepartment of Pediatrics, Texas Children's Cancer Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
H ZhangDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
J Dou1] Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA [2] Xinjiang Key Laboratory of Plant Resources and Natural Products Chemistry, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, Xinjiang 830011, China.
Y Tang1] Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA [2] Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
X Zhong1] Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA [2] Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
Y RojasDivision of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Y YuDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Y ZhaoDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
S A VasudevanDivision of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
H ZhangDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
J G NuchternDivision of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
E S KimDivision of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
X ChenDepartment of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China.
F LuDepartment of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China.
J YangDepartment of Pediatrics, Texas Children's Cancer Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
The University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · USPeking University · CNChildren's Cancer Center · US

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9M
DUSP26: A Novel Therapeutic Target in NeuroblastomaR01NS072420 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI YANG, JIANHUA · 2011 to 2014
$1.4M
Targeting TAK1 in NeuroblastomaR21NS085467 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI YANG, JIANHUA · 2013 to 2014
$430k
NCI NIH HHS P30 CA125123NINDS NIH HHS 1R01NS072420NINDS NIH HHS 1R21NS085467NINDS NIH HHS R01 NS072420NINDS NIH HHS R21 NS085467
6 · The paper itself

Abstract

Neuroblastoma (NB) is the most common extracranial neoplasm in children. In NB, loss of p53 function is largely due to cytoplasmic sequestration rather than mutation. Ubiquitin-conjugating enzyme E2 N (UBE2N), also known as Ubc13, is an E2 ubiquitin-conjugating enzyme that promotes formation of monomeric p53 that results in its cytoplasmic translocation and subsequent loss of function. Therefore, inhibition of UBE2N may reactivate p53 by promoting its nuclear accumulation. Here, we show that NSC697923, a novel UBE2N inhibitor, exhibits potent cytotoxicity in a panel of NB cell lines evidenced by its ability to induce apoptosis. In p53 wild-type NB cells, NSC697923 induced nuclear accumulation of p53, which led to its increased transcriptional activity and tumor suppressor function. Interestingly, in p53 mutant NB cells, NSC697923 induced cell death by activating JNK pathway. This effect was reversible by blocking JNK activity with its selective inhibitor, SP600125. More importantly, NSC697923 impeded cell growth of chemoresistant LA-N-6 NB cell line in a manner greater than conventional chemotherapy drugs doxorubicin and etoposide. NSC697923 also revealed in vivo antitumor efficacy in NB orthotopic xenografts. Taken together, our results suggest that UBE2N is a potential therapeutic target in NB and provide a basis for the rational use of UBE2N inhibitors like NSC697923 as a novel treatment option for NB patients.

Indexed as

Active Transport, Cell NucleusAnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug Resistance, NeoplasmEnzyme ActivationEnzyme InhibitorsFemaleHEK293 CellsHumansJNK Mitogen-Activated Protein KinasesMiceMice, NudeAntineoplastic AgentsEnzyme InhibitorsJNK Mitogen-Activated Protein KinasesProtein Kinase InhibitorsTP53 protein, humanTumor Suppressor Protein p53UBE2N protein, humanUbiquitin-Conjugating Enzymes

Identifiers

PMID24556694
PMCPMC3944268
OpenAlexW2031991695

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.