Evidence map›Paper›PMID 26590164›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016

Unfolded-protein response-associated stabilization of p27(Cdkn1b) interferes with lens fiber cell denucleation, leading to cataract.

Lei Lyu, Elizabeth A Whitcomb, Shuhong Jiang, Min-Lee Chang, Yumei Gu, Melinda K Duncan, Ales Cvekl, Wei-Lin Wang, Saima Limi, Lixing W Reneker and 3 more

Abstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

27 citing papers in PubMed, 32 citations in OpenAlex.

  1. International journal of molecular sciences · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022
    Review
  9. Article
  10. Review
  11. Aged Nrf2-Null Mice Develop All Major Types of Age-Related Cataracts.Investigative ophthalmology & visual science · 2021
    Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Stabilization of p27FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  18. Article
  19. Article
  20. Review
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

13 authors at 6 institutions in 2 countries.

Lei Lyu*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Elizabeth A Whitcomb*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Shuhong Jiang*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Min-Lee Chang*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Yumei Gu*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Melinda K Duncan*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Ales Cvekl*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Wei-Lin Wang*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Saima Limi*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Lixing W Reneker*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Fu Shang*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Linfang Du*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA allen.taylor@tufts.edu dulinfang@scu.edu.cn.
Allen Taylor*Ministry of Education Key Laboratory of Bio-resource and Eco-environment, College of Life Science, Sichuan University, Sichuan China; Laboratory for Nutrition and Vision Research, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA; Department of Biological Sciences, University of Delaware, Newark, Delaware, USA; Department of Genetics and Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, USA; and Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, Missouri, USA allen.taylor@tufts.edu dulinfang@scu.edu.cn.
Jean Mayer Human Nutrition Research Center on Aging · USAlbert Einstein College of Medicine · USSichuan University · CNTufts University · USUniversity of Delaware · USUniversity of Missouri · US

Funding

The Influence of Capsule Composition on Lens BiologyR01EY015279 · NEI · UNIVERSITY OF DELAWARE · PI DUNCAN, MELINDA K · 2004 to 2025
$7.8M
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
Ubiquitin function in eye lensR01EY026979 · NEI · TUFTS UNIVERSITY BOSTON · PI TAYLOR, ALLEN · 2016 to 2018
$1.2M
UBIQUITIN DEPENDENT PATHWAY AND LENS EPITHELIUMR29EY011717 · NEI · TUFTS UNIVERSITY BOSTON · PI SHANG, FU · 1998 to 2002
$381k
NEI NIH HHS EY11717NEI NIH HHS EY13250NEI NIH HHS R01 EY011717NEI NIH HHS R01 EY013250NEI NIH HHS R01 EY015279NEI NIH HHS R01 EY026979NEI NIH HHS R29 EY011717
6 · The paper itself

Abstract

Failure of lens fiber cell denucleation (LFCD) is associated with congenital cataracts, but the pathobiology awaits elucidation. Recent work has suggested that mechanisms that direct the unidirectional process of LFCD are analogous to the cyclic processes associated with mitosis. We found that lens-specific mutations that elicit an unfolded-protein response (UPR) in vivo accumulate p27(Cdkn1b), show cyclin-dependent kinase (Cdk)-1 inhibition, retain their LFC nuclei, and are cataractous. Although a UPR was not detected in lenses expressing K6W-Ub, they also accumulated p27 and showed failed LFCD. Induction of a UPR in human lens epithelial cells (HLECs) also induced accumulation of p27 associated with decreased levels of S-phase kinase-associated protein (Skp)-2, a ubiquitin ligase that regulates mitosis. These cells also showed decreased lamin A/C phosphorylation and metaphase arrest. The suppression of lamin A/C phosphorylation and metaphase transition induced by the UPR was rescued by knockdown of p27. Taken together, these data indicate that accumulation of p27, whether related to the UPR or not, prevents the phosphorylation of lamin A/C and LFCD in maturing LFCs in vivo, as well as in dividing HLECs. The former leads to cataract and the latter to metaphase arrest. These results suggest that accumulation of p27 is a common mechanism underlying retention of LFC nuclei.

Indexed as

AnimalsCataractCell LineCell NucleusCyclin-Dependent Kinase Inhibitor p27Epithelial CellsFemaleHumansLamin Type ALens, CrystallineMaleMiceMice, Inbred C57BLMice, TransgenicMitosisPhosphorylationCyclin-Dependent Kinase Inhibitor p27lamin CLamin Type AS-Phase Kinase-Associated Proteinscell cycleendoplasmic reticulum stressnuclear disassemblyubiquitin

Identifiers

PMID26590164
PMCPMC4750420
OpenAlexW2174664303

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.