Evidence map›Paper›PMID 21059646›Full record

ArticleThe Journal of biological chemistry2011

Processing of optineurin in neuronal cells.

Xiang Shen, Hongyu Ying, Ye Qiu, Jeong-Seok Park, Rajalekshmy Shyam, Zai-Long Chi, Takeshi Iwata, Beatrice Y J T Yue

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
4.2field-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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

  1. Pooled it
  2. Protein misfolding and mitochondrial dysfunction in glaucoma.Frontiers in cell and developmental biology · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. The Role of Autophagy in Glaucomatous Optic Neuropathy.Frontiers in cell and developmental biology · 2020
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  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

8 authors at 3 institutions in 2 countries.

Xiang ShenDepartment of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA.
Hongyu Ying
Ye Qiu
Jeong-Seok Park
Rajalekshmy Shyam
Zai-Long Chi
Takeshi Iwata
Beatrice Y J T Yue
University of Illinois Chicago · USNational Hospital Organization · JPUniversity of Illinois Urbana-Champaign · US

Funding

Translational Core for Therapeutic and Diagnostic DevelopmentP30EY001792 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MCANANY, JAMES JASON · 1985 to 2025
$14.8M
BIOLOGY OF TRABECULAR MESHWORK IN HEALTH &DISEASER01EY005628 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI YUE, BEATRICE Y.J.T. · 1985 to 2009
$3.4M
CONNECTIVE TISSUE AND RNA STUDIES OF DISEASED CORNEASR01EY003890 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI YUE, BEATRICE Y.J.T. · 1985 to 2007
$3.0M
Cellular Processing of Optineurin, the Product of a Glaucoma GeneR01EY018828 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI YUE, BEATRICE Y.J.T. · 2009 to 2012
$1.7M
NEI NIH HHS EY003890NEI NIH HHS EY005628NEI NIH HHS EY01792NEI NIH HHS EY018828NEI NIH HHS P30 EY001792NEI NIH HHS R01 EY003890NEI NIH HHS R01 EY005628NEI NIH HHS R01 EY018828
6 · The paper itself

Abstract

Optineurin is a gene linked to amyotrophic lateral sclerosis, Paget disease of bone, and glaucoma, a major blinding disease. Mutations such as E50K were identified in glaucoma patients. We investigated herein the involvement of ubiquitin-proteasome pathway (UPP) and autophagy, two major routes for protein clearance, in processing of optineurin in a retinal ganglion cell model line RGC5 and neuronal PC12 cells. It was found that the endogenous optineurin level in neuronal cells was increased by treatment of proteasomal inhibitor but not by autophagic and lysosomal inhibitors. Multiple bands immunoreactive to anti-ubiquitin were seen in the optineurin pulldown, indicating that optineurin was ubiquitinated. In cells overexpressing wild type and E50K optineurin, the level of the proteasome regulatory β5 subunit (PSMB5, indicative of proteasome activity) was reduced, whereas that for autophagy marker microtubule-associated protein 1 light chain 3 was enhanced compared with controls. Autophagosome formation was detected by electron microscopy. The foci formed after optineurin transfection were increased upon treatment of an autophagic inhibitor but were decreased by treatment of an inducer, rapamycin. Moreover, the level of optineurin-triggered apoptosis was reduced by rapamycin. This study thus provides compelling evidence that in a normal homeostatic situation, the turnover of endogenous optineurin involves mainly UPP. When optineurin is up-regulated or mutated, the UPP function is compromised, and autophagy comes into play. A decreased PSMB5 level and an induced autophagy were also demonstrated in vivo in retinal ganglion cells of E50K transgenic mice, validating and making relevant the in vitro findings.

Indexed as

AutophagyUbiquitinationAnimalsApoptosisCell Cycle ProteinsCell LineEye ProteinsHumansMembrane Transport ProteinsMiceMice, TransgenicNeuronsPC12 CellsProteasome Endopeptidase ComplexRatsRetinaCell Cycle ProteinsEye ProteinsMembrane Transport ProteinsOPTN protein, humanProteasome Endopeptidase ComplexPsmb5 protein, ratTranscription Factor TFIIIA

Identifiers

PMID21059646
PMCPMC3030366
OpenAlexW2084719535

What OpenQuestion holds

Textmetadata
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.