Evidence map›Paper›PMID 22915036›Full record

ArticleInvestigative ophthalmology & visual science2012

Enhancement of ubiquitin conjugation activity reduces intracellular aggregation of V76D mutant γD-crystallin.

Zhenzhen Liu, Allen Taylor, Yizhi Liu, Mingxing Wu, Xiaohua Gong, Fu Shang

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

Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact, top 95% 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

5 citing papers in PubMed, 8 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

6 authors at 4 institutions in 2 countries.

Zhenzhen LiuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Allen Taylor
Yizhi Liu
Mingxing Wu
Xiaohua Gong
Fu Shang
Sun Yat-sen University · CNTufts University · USJean Mayer Human Nutrition Research Center on Aging · USUniversity of California, Berkeley · US

Funding

Cataracts, Connexin Mutants and Genetic ModifiersR01EY013849 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI Xiaohua Gong · 2002 to 2026
$8.2M
Ubiquitin Function In Eye LensR01EY013250 · NEI · TUFTS UNIVERSITY BOSTON · PI TAYLOR, ALLEN · 2001 to 2012
$4.0M
Role of ubiqutin in quality control of lens proteinsR01EY011717 · NEI · TUFTS UNIVERSITY BOSTON · PI SHANG, FU · 2003 to 2010
$1.8M
Mechanistically linking AMD, glycemic index and protein homeostasisR01EY021212 · NEI · TUFTS UNIVERSITY BOSTON · PI TAYLOR, ALLEN · 2011 to 2013
$1.2M
UBIQUITIN DEPENDENT PATHWAY AND LENS EPITHELIUMR29EY011717 · NEI · TUFTS UNIVERSITY BOSTON · PI SHANG, FU · 1998 to 2002
$381k
NEI NIH HHS EY 011717NEI NIH HHS EY 013250NEI NIH HHS EY 021212NEI NIH HHS R01 EY011717NEI NIH HHS R01 EY013250NEI NIH HHS R01 EY013849NEI NIH HHS R01 EY021212NEI NIH HHS R29 EY011717
6 · The paper itself

Abstract

purposeThe ubiquitin-proteasome pathway (UPP) is an important protein quality control mechanism for selective degradation of abnormal proteins. The objective of this study was to test the hypothesis that enhancement of the UPP capacity could attenuate the accumulation and aggregation of misfolded proteins using V76D-γD-crystallin as a model substrate.

methodsWild type (wt) and V76D mutant γD-crystallin were fused to red fluorescence protein (RFP) and expressed in human lens epithelial cells. The cellular distribution of the expressed proteins was compared by fluorescence microscopy. The solubility of wt- and V76D-γD-crystallin was determined by cellular fractionation and Western blotting. Wt-γD-RFP and V76D-γD-RFP were also cotransfected along with a ubiquitin ligase (CHIP) or a ubiquitin-conjugating enzyme (Ubc5) into cells. Levels of wt- and V76D-γD-crystallin, the percentage of transfected cells with aggregates, and aggregate size were quantified and compared among different groups.

resultsWt-γD-crystallin was evenly distributed in cells, whereas V76D-γD-crystallin formed intracellular aggregates. Eighty percent of wt-γD-crystallin was detected in the soluble fraction, whereas only 7% of V76D-γD-crystallin was soluble. CHIP or Ubc5 coexpression reduced the protein level of V76D-γD and concomitantly its aggregation in transfected cells; these effects could be attenuated by proteasome inhibitor. Mutant CHIP with defect TPR (tetratricopeptide repeat) or U-box domain failed to reduce levels of V76D-γD-crystallin.

conclusionsEnhancing ubiquitin conjugation activity reduces accumulation and aggregation of V76D-γD-crystallin by promoting its degradation. Upregulation of ubiquitin-conjugating activity could be an effective strategy to maintain lens transparency by eliminating other forms of misfolded proteins.

Indexed as

Mutation, MissenseBlotting, WesternElectrophoresis, Polyacrylamide GelEpithelial Cellsgamma-CrystallinsGene ExpressionHeLa CellsHumansLens, CrystallineLeupeptinsLuminescent ProteinsMicroscopy, FluorescencePlasmidsProtein FoldingRed Fluorescent ProteinSolubilitybenzyloxycarbonylleucyl-leucyl-leucine aldehydeCRYGD protein, humangamma-CrystallinsLeupeptinsLuminescent ProteinsRed Fluorescent ProteinSTUB1 protein, humanUBE2D1 protein, humanUbiquitin-Conjugating EnzymesUbiquitin-Protein Ligase ComplexesUbiquitin-Protein Ligases

Identifiers

PMID22915036
PMCPMC3460391
OpenAlexW1963501900

What OpenQuestion holds

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Registered trials

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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.