ArticleThe Journal of biological chemistry2009
Dominant-negative effects of COL7A1 mutations can be rescued by controlled overexpression of normal collagen VII.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 44 citations in OpenAlex.
- Twin Prime Editing Mediated Exon Skipping/Reinsertion for Restored Collagen VII Expression in Recessive Dystrophic Epidermolysis Bullosa.The Journal of investigative dermatology · 2024Article
- The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy.Journal of biomedical science · 2024Review
- Mutant collagen COL11A1 enhances cancerous invasion.Oncogene · 2021Article
- Clinical Perspectives of Gene-Targeted Therapies for Epidermolysis Bullosa.Dermatology and therapy · 2021Review
- Challenges in Treating Genodermatoses: New Therapies at the Horizon.Frontiers in pharmacology · 2021Review
- Natural Exon Skipping Sets the Stage for Exon Skipping as Therapy for Dystrophic Epidermolysis Bullosa.Molecular therapy. Nucleic acids · 2019Article
- Basement membranes in the cornea and other organs that commonly develop fibrosis.Cell and tissue research · 2018Review
- RNA-based therapies for genodermatoses.Experimental dermatology · 2017Review
- Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Efficient Targeted Next Generation Sequencing-Based Workflow for Differential Diagnosis of Alport-Related Disorders.PloS one · 2016Article
- Trans-splicing improvement by the combined application of antisense strategies.International journal of molecular sciences · 2015Article
- Missense mutations in pyruvate kinase M2 promote cancer metabolism, oxidative endurance, anchorage independence, and tumor growth in a dominant negative manner.The Journal of biological chemistry · 2014Article
- Collagen VII plays a dual role in wound healing.The Journal of clinical investigation · 2013Article
- Article
- Skin basement membrane: the foundation of epidermal integrity--BM functions and diverse roles of bridging molecules nidogen and perlecan.BioMed research international · 2013Review
- Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases.BMC immunology · 2012Article
- Remodeling of the dermal-epidermal junction in bilayered skin constructs after silencing the expression of the p.R2622Q and p.G2623C collagen VII mutants.Connective tissue research · 2012Article
- A cellular model for the investigation of Fuchs' endothelial corneal dystrophy.Experimental eye research · 2011Article
- Persistence of intracellular and extracellular changes after incompletely suppressing expression of the R789C (p.R989C) and R992C (p.R1192C) collagen II mutants.Human mutation · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dominant-negative interference by glycine substitution mutations in the COL7A1 gene causes dominant dystrophic epidermolysis bullosa (DDEB), a skin fragility disorder with mechanically induced blistering. Although qualitative and quantitative alterations of the COL7A1 gene product, collagen VII, underlie DDEB, the lack of direct correlation between mutations and the clinical phenotype has rendered DDEB less amenable to therapeutic targeting. To delineate the molecular mechanisms of DDEB, we used recombinant expression of wild-type (WT) and mutant collagen VII, which contained a naturally occurring COL7A1 mutation, G1776R, G2006D, or G2015E, for characterization of the triple helical molecules. The mutants were co-expressed with WT in equal amounts and could form heterotrimeric hybrid triple helices, as demonstrated by affinity purification and mass spectrometry. The thermal stability of the mutant molecules was strongly decreased, as evident in their sensitivity to trypsin digestion. The helix-to-coil transition, T(m), of the mutant molecules was 31-34 degrees C, and of WT collagen VII 41 degrees C. Co-expression of WT with G1776R- or G2006D-collagen VII resulted in partial intracellular retention of the collagen, and mutant collagen VII had reduced ability to support cell adhesion. Intriguingly, controlled overexpression of WT collagen VII gradually improved the thermal stability of the collective of collagen VII molecules. Co-expression in a ratio of 90% WT:10% mutant increased the T(m) to 41 degrees C for G1776R-collagen VII and to 39 degrees C for G2006D- and G2015E-collagen VII. Therefore, increasing the expression of WT collagen VII in the skin of patients with DDEB can be considered a valid therapeutic approach.
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