ArticleMolecular biology of the cell2010
Lens fiber cell differentiation and denucleation are disrupted through expression of the N-terminal nuclear receptor box of NCOA6 and result in p53-dependent and p53-independent apoptosis.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Phosphorylated NCOA6 promotes aggressiveness and contributes patient outcomes in estrogen receptor-positive breast cancer.Cancer cell international · 2025Article
- Nucleolar ribosomal RNA synthesis continues in differentiating lens fiber cells until abrupt nuclear degradation required for ocular lens transparency.RNA biology · 2025Review
- Analysis of long-range chromatin contacts, compartments and looping between mouse embryonic stem cells, lens epithelium and lens fibers.Epigenetics & chromatin · 2024Article
- SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.Aging · 2023Article
- A tamoxifen-inducible Cre knock-in mouse for lens-specific gene manipulation.Experimental eye research · 2023Article
- Review
- Article
- More Than Meets the Eye: Revisiting the Roles of Heat Shock Factor 4 in Health and Diseases.Biomolecules · 2021Review
- Application of WES Towards Molecular Investigation of Congenital Cataracts: Identification of Novel Alleles and Genes in a Hospital-Based Cohort of South India.International journal of molecular sciences · 2020Article
- HSF4 regulates lens fiber cell differentiation by activating p53 and its downstream regulators.Cell death & disease · 2017Article
- Disassembly of the lens fiber cell nucleus to create a clear lens: The p27 descent.Experimental eye research · 2017Review
- Chromatin remodeling enzyme Snf2h regulates embryonic lens differentiation and denucleation.Development (Cambridge, England) · 2016Article
- Human βA3/A1-crystallin splicing mutation causes cataracts by activating the unfolded protein response and inducing apoptosis in differentiating lens fiber cells.Biochimica et biophysica acta · 2016Article
- Mutations of RagA GTPase in mTORC1 Pathway Are Associated with Autosomal Dominant Cataracts.PLoS genetics · 2016Article
- Unfolded-protein response-associated stabilization of p27(Cdkn1b) interferes with lens fiber cell denucleation, leading to cataract.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Pax6 associates with H3K4-specific histone methyltransferases Mll1, Mll2, and Set1a and regulates H3K4 methylation at promoters and enhancers.Epigenetics & chromatin · 2016Article
- MLL3 and MLL4 Methyltransferases Bind to the MAFA and MAFB Transcription Factors to Regulate Islet β-Cell Function.Diabetes · 2015Article
- Aberrant activation of p53 due to loss of MDM2 or MDMX causes early lens dysmorphogenesis.Developmental biology · 2014Article
- The cellular and molecular mechanisms of vertebrate lens development.Development (Cambridge, England) · 2014Review
- Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly.Development (Cambridge, England) · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Nuclear receptor coactivator 6 (NCOA6) is a multifunctional protein implicated in embryonic development, cell survival, and homeostasis. An 81-amino acid fragment, dnNCOA6, containing the N-terminal nuclear receptor box (LXXLL motif) of NCOA6, acts as a dominant-negative (dn) inhibitor of NCOA6. Here, we expressed dnNCOA6 in postmitotic transgenic mouse lens fiber cells. The transgenic lenses showed reduced growth; a wide spectrum of lens fiber cell differentiation defects, including reduced expression of gamma-crystallins; and cataract formation. Those lens fiber cells entered an alternate proapoptotic pathway, and the denucleation (karyolysis) process was stalled. Activation of caspase-3 at embryonic day (E)13.5 was followed by double-strand breaks (DSBs) formation monitored via a biomarker, gamma-H2AX. Intense terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) signals were found at E16.5. Thus, a window of approximately 72 h between these events suggested prolonged though incomplete apoptosis in the lens fiber cell compartment that preserved nuclei in its cells. Genetic experiments showed that the apoptotic-like processes in the transgenic lens were both p53-dependent and p53-independent. Lens-specific deletion of Ncoa6 also resulted in disrupted lens fiber cell differentiation. Our data demonstrate a cell-autonomous role of Ncoa6 in lens fiber cell differentiation and suggest novel insights into the process of lens fiber cell denucleation and apoptosis.
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