Evidence map›Paper›PMID 27086925›Full record

ArticleOncogene2016

A novel nickel complex works as a proteasomal deubiquitinase inhibitor for cancer therapy.

C Zhao, X Chen, D Zang, X Lan, S Liao, C Yang, P Zhang, J Wu, X Li, N Liu and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. The 19S proteasome as a therapeutic target in hematologic malignancies.Frontiers in cell and developmental biology · 2026
    Review
  5. Review
  6. Review
  7. Recent advances in copper homeostasis-involved tumor theranostics.Asian journal of pharmaceutical sciences · 2024
    Review
  8. Review
  9. Article
  10. A second chance for protein targeting/folding: Ubiquitination and deubiquitination of nascent proteins.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors.International journal of molecular sciences · 2021
    Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. 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

19 authors at 3 institutions in 2 countries.

C ZhaoState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
X ChenState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
D ZangState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
X LanState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
S LiaoState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
C YangState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
P ZhangState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
J WuState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
X LiState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
N LiuState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
Y LiaoState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
H HuangState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
X ShiState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
L JiangState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
X LiuInstitute of Environmental and Analytical Sciences, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, China.
Z HeCancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou, China.
Q P DouThe Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
X WangState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
J LiuState Key Lab of Respiratory Disease, Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
Guangzhou Medical University · CNHenan University · CNThe Barbara Ann Karmanos Cancer Institute · US

Funding

Ubiquitin receptors and cardiac proteotoxicityR01HL072166 · NHLBI · UNIVERSITY OF SOUTH DAKOTA · PI WANG, XUEJUN · 2003 to 2023
$6.9M
The COP9 SIgnalosome in the HeartR01HL085629 · NHLBI · UNIVERSITY OF SOUTH DAKOTA · PI WANG, XUEJUN · 2006 to 2019
$4.7M
(PQA1) Regulation of Metformin Response by Breast Cancer Associated Gene 2 (BCA2)R21CA184788 · NCI · WAYNE STATE UNIVERSITY · PI DOU, QING PING · 2014 to 2015
$364k
NCI NIH HHS R21 CA184788NHLBI NIH HHS R01 HL072166NHLBI NIH HHS R01 HL085629
6 · The paper itself

Abstract

Based on the central role of the ubiquitin-proteasome system (UPS) in the degradation of cellular proteins, proteasome inhibition has been considered an attractive approach for anticancer therapy. Deubiquitinases (DUBs) remove ubiquitin conjugates from diverse substrates; therefore, they are essential regulators of the UPS. DUB inhibitors, especially the inhibitors of proteasomal DUBs are becoming a research hotspot in targeted cancer therapy. Previous studies have shown that metal complexes, such as copper and zinc complexes, can induce cancer cell apoptosis through inhibiting UPS function. Moreover, we have found that copper pyrithione inhibits both 19S proteasome-associated DUBs and 20S proteasome activity with a mechanism distinct from that of the classical 20S proteasome inhibitor bortezomib. In the present study, we reveal that (i) nickel pyrithione complex (NiPT) potently inhibits the UPS via targeting the 19S proteasome-associated DUBs (UCHL5 and USP14), without effecting on the 20S proteasome; (ii) NiPT selectively induces proteasome inhibition and apoptosis in cultured tumor cells and cancer cells from acute myeloid leukemia human patients; and (iii) NiPT inhibits proteasome function and tumor growth in nude mice. This study, for the first time, uncovers a nickel complex as an effective inhibitor of the 19S proteasomal DUBs and suggests a potentially new strategy for cancer treatment.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCell SurvivalDisease Models, AnimalDNA DamageHumansMembrane Potential, MitochondrialMiceNickelProteasome Endopeptidase ComplexProteasome InhibitorsTumor BurdenUbiquitinAntineoplastic AgentsNickelProteasome Endopeptidase ComplexProteasome InhibitorsUbiquitin

Identifiers

PMID27086925
PMCPMC5497060
OpenAlexW2340350163

What OpenQuestion holds

Textmetadata
LicenceTDM
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.