ArticleHuman molecular genetics2014
iRHOM2-dependent regulation of ADAM17 in cutaneous disease and epidermal barrier function.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 82 citations in OpenAlex.
- Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease.Nature immunology · 2022Trial
- Structural basis for ADAM17 activation by the iRhom1 pseudoprotease.Cell reports · 2026Article
- Review
- Proteolytic dysregulation in the skin: insight from rare monogenic skin diseases.Cell and tissue research · 2026Review
- Article
- ADAM Proteases in Cancer: Biological Roles, Therapeutic Challenges, and Emerging Opportunities.Cancers · 2025Review
- Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.Cellular and molecular life sciences : CMLS · 2024Article
- Cleavage of the pseudoprotease iRhom2 by the signal peptidase complex reveals an ER-to-nucleus signaling pathway.Molecular cell · 2024Article
- Investigating iRHOM2-Associated Transcriptional Changes in Tylosis With Esophageal Cancer.Gastro hep advances · 2024Article
- Nucleic acid-based nanotherapeutics for treating sepsis and associated organ injuries.Theranostics · 2024Review
- Analysis of the function of ADAM17 in iRhom2 curly-bare and tylosis with esophageal cancer mutant mice.Journal of cell science · 2023Article
- Inhibiting EGFR Signaling Holds Promise for Treating Palmoplantar Keratodermas.The Journal of investigative dermatology · 2023Article
- iRhom2 regulates ERBB signalling to promote KRAS-driven tumour growth of lung cancer cells.Journal of cell science · 2022Article
- Immunomodulatory role of metalloproteinase ADAM17 in tumor development.Frontiers in immunology · 2022Review
- Investigating isoform switching inPeerJ · 2022Article
- ADAM17 Mediates Hypoxia-Induced Keratinocyte Migration via the p38/MAPK Pathway.BioMed research international · 2021Article
- Polarization of ADAM17-driven EGFR signalling in electric field-guided collective migration of epidermal sheets.Journal of cellular and molecular medicine · 2020Article
- iRhom2: An Emerging Adaptor Regulating Immunity and Disease.International journal of molecular sciences · 2020Review
- iRhom2 in the pathogenesis of oral squamous cell carcinoma.Molecular biology reports · 2020Article
- Deletion of iRhom2 protects against diet-induced obesity by increasing thermogenesis.Molecular metabolism · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
iRHOM2 is a highly conserved, catalytically inactive member of the Rhomboid family, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 (TACE) in macrophages. Dominant iRHOM2 mutations are the cause of the inherited cutaneous and oesophageal cancer-susceptibility syndrome tylosis with oesophageal cancer (TOC), suggesting a role for this protein in epithelial cells. Here, using tissues derived from TOC patients, we demonstrate that TOC-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes, resulting in significantly upregulated shedding of ADAM17 substrates, including EGF-family growth factors and pro-inflammatory cytokines. This activity is accompanied by increased EGFR activity, increased desmosome processing and the presence of immature epidermal desmosomes, upregulated epidermal transglutaminase activity and heightened resistance to Staphylococcal infection in TOC keratinocytes. Many of these features are consistent with the presence of a constitutive wound-healing-like phenotype in TOC epidermis, which may shed light on a novel pathway in skin repair, regeneration and inflammation.
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Registered trials
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.