ArticleProceedings of the National Academy of Sciences of the United States of America2001
Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 129 citations in OpenAlex.
- Ectodysplasin-A (EDA) Signaling Cross-Talk in Skeletogenesis.Calcified tissue international · 2026Review
- Mutational spectrum of EDA, EDAR, EDARADD, and WNT10A genes in the largest cohort of Russian patients with hypohidrotic ectodermal dysplasia.Orphanet journal of rare diseases · 2026Article
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- Furin extracellularly cleaves secreted PTENα/β to generate C-terminal fragment with a tumor-suppressive role.Cell death & disease · 2022Article
- Evidence of Selection in the Ectodysplasin Pathway among Endangered Aquatic Mammals.Integrative organismal biology (Oxford, England) · 2022Article
- Two novel ectodysplasin A gene mutations and prenatal diagnosis of X-linked hypohidrotic ectodermal dysplasia.Molecular genetics & genomic medicine · 2021Article
- Increased Circulating Levels of Ectodysplasin A in Newly Diagnosed Type 2 Diabetic Patients.Frontiers in endocrinology · 2021Article
- Ectodysplasin A Is Increased in Non-Alcoholic Fatty Liver Disease, But Is Not Associated With Type 2 Diabetes.Frontiers in endocrinology · 2021Article
- Fetal gene therapy and pharmacotherapy to treat congenital hearing loss and vestibular dysfunction.Hearing research · 2020Review
- AG3 (Bethesda, Md.) · 2019Article
- Furin-mediated protein processing in infectious diseases and cancer.Clinical & translational immunology · 2019Review
- Ectodysplasin A protein promotes corneal epithelial cell proliferation.The Journal of biological chemistry · 2017Article
- TNF superfamily cytokines in the promotion of Th9 differentiation and immunopathology.Seminars in immunopathology · 2017Review
- Molecular basis of hypohidrotic ectodermal dysplasia: an update.Journal of applied genetics · 2016Review
- RETRACTED: Functional Study of Ectodysplasin-A Mutations Causing Non-Syndromic Tooth Agenesis.PloS one · 2016Article
- Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.The Journal of biological chemistry · 2014Article
- The sequence flanking the N-terminus of the CLV3 peptide is critical for its cleavage and activity in stem cell regulation in Arabidopsis.BMC plant biology · 2013Article
- Mutations in endothelin 1 cause recessive auriculocondylar syndrome and dominant isolated question-mark ears.American journal of human genetics · 2013Article
- Transcriptome sequencing and annotation for the Jamaican fruit bat (Artibeus jamaicensis).PloS one · 2012Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
X-linked hypohidrotic ectodermal dysplasia (XLHED) is a heritable disorder of the ED-1 gene disrupting the morphogenesis of ectodermal structures. The ED-1 gene product, ectodysplasin-A (EDA), is a tumor necrosis factor (TNF) family member and is synthesized as a membrane-anchored precursor protein with the TNF core motif located in the C-terminal domain. The stalk region of EDA contains the sequence -Arg-Val-Arg-Arg156-Asn-Lys-Arg159-, representing overlapping consensus cleavage sites (Arg-X-Lys/Arg-Arg( downward arrow)) for the proprotein convertase furin. Missense mutations in four of the five basic residues within this sequence account for approximately 20% of all known XLHED cases, with mutations occurring most frequently at Arg156, which is shared by the two consensus furin sites. These analyses suggest that cleavage at the furin site(s) in the stalk region is required for the EDA-mediated cell-to-cell signaling that regulates the morphogenesis of ectodermal appendages. Here we show that the 50-kDa EDA parent molecule is cleaved at -Arg156Asn-Lys-Arg(159 downward arrow)- to release the soluble C-terminal fragment containing the TNF core domain. This cleavage appears to be catalyzed by furin, as release of the TNF domain was blocked either by expression of the furin inhibitor alpha1-PDX or by expression of EDA in furin-deficient LoVo cells. These results demonstrate that mutation of a functional furin cleavage site in a developmental signaling molecule is a basis for human disease (XLHED) and raise the possibility that furin cleavage may regulate the ability of EDA to act as a juxtacrine or paracrine factor.
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