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.
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.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- The Mammalian Ocular Lens in Focus: Development, Anatomy, Physiology, Transparency, Biomechanics, and Age-related Challenges.Journal of visualized experiments : JoVE · 2026Review
- Analysis of long-range chromatin contacts, compartments and looping between mouse embryonic stem cells, lens epithelium and lens fibers.Epigenetics & chromatin · 2024Article
- Identification of immune-related endoplasmic reticulum stress genes in proliferative diabetic retinopathy using bioinformatics analysis.Frontiers in endocrinology · 2024Article
- The involvement of caspases in the process of nuclear removal during lens fiber cell differentiation.Cell death discovery · 2023Article
- Unbalanced redox status network as an early pathological event in congenital cataracts.Redox biology · 2023Article
- Repurposing a Cyclin-Dependent Kinase 1 (CDK1) Mitotic Regulatory Network to Complete Terminal Differentiation in Lens Fiber Cells.Investigative ophthalmology & visual science · 2023Article
- Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022Review
- Suppression of PI3K signaling is linked to autophagy activation and the spatiotemporal induction of the lens organelle free zone.Experimental cell research · 2022Article
- A possible connection between reactive oxygen species and the unfolded protein response in lens development: From insight to foresight.Frontiers in cell and developmental biology · 2022Review
- Aged Nrf2-Null Mice Develop All Major Types of Age-Related Cataracts.Investigative ophthalmology & visual science · 2021Article
- Mechanisms of organelle elimination for lens development and differentiation.Experimental eye research · 2021Review
- Inherited cataracts: Genetic mechanisms and pathways new and old.Experimental eye research · 2021Review
- A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis.BMC genomics · 2021Article
- Crystallin gene expression: Insights from studies of transcriptional bursting.Experimental eye research · 2021Review
- Lens regeneration in humans: using regenerative potential for tissue repairing.Annals of translational medicine · 2020Review
- Stabilization of p27FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- BNIP3L/NIX is required for elimination of mitochondria, endoplasmic reticulum and Golgi apparatus during eye lens organelle-free zone formation.Experimental eye research · 2018Article
- The RNA-binding protein Celf1 post-transcriptionally regulates p27Kip1 and Dnase2b to control fiber cell nuclear degradation in lens development.PLoS genetics · 2018Article
- Association between endoplasmic reticulum stress and risk factors of diabetic retinopathy.International journal of ophthalmology · 2018Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
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.
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