Evidence map›Paper›PMID 27626314›Full record

ArticleOncotarget2016

The ubiquitin ligase TRIM25 targets ERG for degradation in prostate cancer.

Shan Wang, Rahul K Kollipara, Caroline G Humphries, Shi-Hong Ma, Ryan Hutchinson, Rui Li, Javed Siddiqui, Scott A Tomlins, Ganesh V Raj, Ralf Kittler

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

24 citing papers in PubMed, 44 citations in OpenAlex.

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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

10 authors at 4 institutions in 1 country.

Shan WangEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Rahul K KolliparaEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Caroline G HumphriesEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Shi-Hong MaDepartment of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Ryan HutchinsonDepartment of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Rui LiDepartment of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Javed SiddiquiDepartment of Pathology, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Scott A TomlinsDepartment of Pathology, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Ganesh V RajDepartment of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Ralf KittlerEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
The University of Texas Southwestern Medical Center · USMichigan Center for Translational Pathology · USSouthwestern Medical Center · USUniversity of Michigan–Ann Arbor · US

Funding

Development of small molecules for ERG ablation in prostate cancerR01CA200787 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI KITTLER, RALF · 2016 to 2020
$1.8M
NCI NIH HHS R01 CA200787
6 · The paper itself

Abstract

Ets related gene (ERG) is a transcription factor that is overexpressed in 40% of prostate tumors due to a gene fusion between ERG and TMPRSS2. Because ERG functions as a driver of prostate carcinogenesis, understanding the mechanisms that influence its turnover may provide new molecular handles to target the protein. Previously, we found that ERG undergoes ubiquitination and then is deubiquitinated by USP9X in prostate cancer cells to prevent its proteasomal degradation. Here, we identify Tripartite motif-containing protein 25 (TRIM25) as the E3 ubiquitin ligase that ubiquitinates the protein prior to its degradation. TRIM25 binds full-length ERG, and it also binds the N-terminally truncated variants of ERG that are expressed in tumors with TMPRSS2-ERG fusions. We demonstrate that TRIM25 polyubiquitinates ERG in vitro and that inactivation of TRIM25 resulted in reduced polyubiquitination and stabilization of ERG. TRIM25 mRNA and protein expression was increased in ERG rearrangement-positive prostate cancer specimens, and we provide evidence that ERG upregulates TRIM25 expression. Thus, overexpression of ERG in prostate cancer may cause an increase in TRIM25 activity, which is mitigated by the expression of the deubiquitinase USP9X, which is required to stabilize ERG.

Indexed as

Cell Line, TumorHEK293 CellsHumansMaleMolecular Targeted TherapyOncogene Proteins, FusionProstatic NeoplasmsProtein BindingProteolysisRNA, Small InterferingSerine EndopeptidasesTranscriptional Regulator ERGTranscription FactorsTripartite Motif ProteinsUbiquitinationUbiquitin-Protein LigasesERG protein, humanOncogene Proteins, FusionRNA, Small InterferingSerine EndopeptidasesTMPRSS2 protein, humanTranscriptional Regulator ERGTranscription FactorsTRIM25 protein, humanTripartite Motif ProteinsUbiquitin-Protein LigasesUbiquitin ThiolesteraseUSP9X protein, humanoncogeneprostate cancertranscription factorubiquitination

Identifiers

PMID27626314
PMCPMC5323126
OpenAlexW2515504521

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.