Evidence map›Paper›PMID 24987841›Full record

ArticlePloS one2014

Loss of urokinase receptor sensitizes cells to DNA damage and delays DNA repair.

Pavan B Narayanaswamy, Mahshid Hodjat, Hermann Haller, Inna Dumler, Yulia Kiyan

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 2 pooled it
1.0field-weighted citation impact, top 26% 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

12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 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

5 authors at 1 institution in 1 country.

Pavan B NarayanaswamyNephrology Department, Hannover Medical School, Hannover, Germany.
Mahshid HodjatNephrology Department, Hannover Medical School, Hannover, Germany.
Hermann HallerNephrology Department, Hannover Medical School, Hannover, Germany.
Inna DumlerNephrology Department, Hannover Medical School, Hannover, Germany.
Yulia KiyanNephrology Department, Hannover Medical School, Hannover, Germany.
Medizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA damage induced by numerous exogenous or endogenous factors may have irreversible consequences on the cell leading to cell cycle arrest, senescence and cell death. The DNA damage response (DDR) is powerful signaling machinery triggered in response to DNA damage, to provide DNA damage recognition, signaling and repair. Most anticancer drugs induce DNA damage, and DNA repair in turn attenuates therapeutic efficiency of those drugs. Approaches delaying DNA repair are often used to increase efficiency of treatment. Recent data show that ubiquitin-proteasome system is essential for signaling and repair of DNA damage. However, mechanisms providing regulation of proteasome intracellular localization, activity, and recruitment to DNA damage sites are elusive. Even less investigated are the roles of extranuclear signaling proteins in these processes. In this study, we report the involvement of the serine protease urokinase-type plasminogen activator receptor (uPAR) in DDR-associated regulation of proteasome. We show that in vascular smooth muscle cells (VSMC) uPAR activates DNA single strand break repair signaling pathway. We provide evidence that uPAR is essential for functional assembly of the 26S proteasome. We further demonstrate that uPAR mediates DNA damage-induced phosphorylation, nuclear import, and recruitment of the regulatory subunit PSMD6 to proteasome. We found that deficiency of uPAR and PSMD6 delays DNA repair and leads to decreased cell survival. These data may offer new therapeutic approaches for diseases such as cancer, cardiovascular and neurodegenerative disorders.

Indexed as

DNA Breaks, Single-StrandedDNA RepairActive Transport, Cell NucleusAnimalsCell LineCells, CulturedCell SurvivalGene DeletionHumansMice, Inbred C57BLMuscle, Smooth, VascularProteasome Endopeptidase ComplexReceptors, Urokinase Plasminogen ActivatorProteasome Endopeptidase ComplexReceptors, Urokinase Plasminogen Activator

Identifiers

PMID24987841
PMCPMC4079571
OpenAlexW1971588556

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.