ArticleThe Journal of clinical investigation2013
Desmoglein-1/Erbin interaction suppresses ERK activation to support epidermal differentiation.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 139 citations in OpenAlex.
- The skin-specific long non-coding RNA TEDAR orchestrates late epidermal differentiation via an ERK-KLF4 cytoplasmic regulatory axis.Cell death & disease · 2026Article
- Interleukin 4-driven loss of stromal LIF signaling affects immune responses and cell-cell adhesion in atopic dermatitis.iScience · 2026Article
- Desmosomal-Type Acantholysis-A New Histologic Pattern Related to Mutations of Genes for Desmosomal Proteins.Dermatopathology (Basel, Switzerland) · 2026Article
- Post translational Modifications and Protein-Protein Interactome of Endemic Pemphigus in El Bagre, Colombia: A New Variant Analysis.Dermatology practical & conceptual · 2025Article
- Pumping the Breaks on Acantholytic Skin Disorders: Targeting Calcium Pumps, Desmosomes, and Downstream Signaling in Darier, Hailey-Hailey, and Grover Disease.The Journal of investigative dermatology · 2025Review
- Ephrin-Eph signaling: an important regulator of epithelial integrity and barrier function.Tissue barriers · 2025Review
- ERK hyperactivation in epidermal keratinocytes impairs intercellular adhesion and drives Grover disease pathology.JCI insight · 2024Article
- Desmosomes at a glance.Journal of cell science · 2024Review
- Unraveling the Mechanisms Involved in the Beneficial Effects of Magnesium Treatment on Skin Wound Healing.International journal of molecular sciences · 2024Article
- Hereditary epidermolytic palmoplantar keratosis due to a novel desmoglein-1 mutation: A case report.Clinical case reports · 2024Article
- Proximity Mapping of Desmosomes Reveals a Striking Shift in Their Molecular Neighborhood Associated With Maturation.Molecular & cellular proteomics : MCP · 2024Article
- Erbin: an important therapeutic target for blocking tumor metastasis.Frontiers in pharmacology · 2024Article
- A desmosomal cadherin controls multipotent hair follicle stem cell quiescence and orchestrates regeneration through adhesion signaling.iScience · 2023Article
- Melanoma cells repress Desmoglein 1 in keratinocytes to promote tumor cell migration.The Journal of cell biology · 2023Article
- Targeting SERCA2 in organotypic epidermis reveals MEK inhibition as a therapeutic strategy for Darier disease.JCI insight · 2023Article
- Desmoglein 2 Functions as a Receptor for Fatty Acid Binding Protein 4 in Breast Cancer Epithelial Cells.Molecular cancer research : MCR · 2023Article
- Dynamic states of cervical epithelia during pregnancy and epithelial barrier disruption.iScience · 2023Article
- Mechanistic Contributions of lncRNAs to Cellular Signaling Pathways Crucial to the Lifecycle of Human Papillomaviruses.Viruses · 2022Review
- FAM167A is a key molecule to induce BCR-ABL-independent TKI resistance in CML via noncanonical NF-κB signaling activation.Journal of experimental & clinical cancer research : CR · 2022Article
- Long non-coding RNAs in diabetic wound healing: Current research and clinical relevance.International wound journal · 2022Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Genetic disorders of the Ras/MAPK pathway, termed RASopathies, produce numerous abnormalities, including cutaneous keratodermas. The desmosomal cadherin, desmoglein-1 (DSG1), promotes keratinocyte differentiation by attenuating MAPK/ERK signaling and is linked to striate palmoplantar keratoderma (SPPK). This raises the possibility that cutaneous defects associated with SPPK and RASopathies share certain molecular faults. To identify intermediates responsible for executing the inhibition of ERK by DSG1, we conducted a yeast 2-hybrid screen. The screen revealed that Erbin (also known as ERBB2IP), a known ERK regulator, binds DSG1. Erbin silencing disrupted keratinocyte differentiation in culture, mimicking aspects of DSG1 deficiency. Furthermore, ERK inhibition and the induction of differentiation markers by DSG1 required both Erbin and DSG1 domains that participate in binding Erbin. Erbin blocks ERK signaling by interacting with and disrupting Ras-Raf scaffolds mediated by SHOC2, a protein genetically linked to the RASopathy, Noonan-like syndrome with loose anagen hair (NS/LAH). DSG1 overexpression enhanced this inhibitory function, increasing Erbin-SHOC2 interactions and decreasing Ras-SHOC2 interactions. Conversely, analysis of epidermis from DSG1-deficient patients with SPPK demonstrated increased Ras-SHOC2 colocalization and decreased Erbin-SHOC2 colocalization, offering a possible explanation for the observed epidermal defects. These findings suggest a mechanism by which DSG1 and Erbin cooperate to repress MAPK signaling and promote keratinocyte differentiation.
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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.