ArticleThe Journal of biological chemistry2014
Receptor-interacting protein kinase 4 and interferon regulatory factor 6 function as a signaling axis to regulate keratinocyte differentiation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 60 citations in OpenAlex.
- Deep Phenotyping and Molecular Elucidation of a New Syndrome: Ectodermal Dysplasia Caused by IRF6 Variants.Experimental dermatology · 2026Article
- IRF6 C-terminal phosphorylation links inflammation and cell-cell adhesion in oral keratinocytes: implications for oral lichen planus.BMC immunology · 2025Article
- Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy.American journal of human genetics · 2025Article
- Inhibition of the RIPK4 enhances suppression of human melanoma growth through vitamin D signaling.Molecular and cellular endocrinology · 2025Article
- IRF6 controls Epstein-Barr virus (EBV) lytic reactivation and differentiation in EBV-infected epithelial cells.PLoS pathogens · 2025Article
- IRF6 Enhances IFN-β Expression and Inhibits Viral Replication to Reduce the Severity of Herpetic Stromal Keratitis.Journal of inflammation research · 2025Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Interferon regulatory factor 6 (IRF6) determines intestinal epithelial cell development and immunity.Mucosal immunology · 2024Article
- The involvement of RIPK4 in TNF-α-stimulated IL-6 and IL-8 production by melanoma cells.Journal of cancer research and clinical oncology · 2024Article
- Functions of the RIP kinase family members in the skin.Cellular and molecular life sciences : CMLS · 2023Review
- Article
- Negative regulation of interferon regulatory factor 6 (IRF6) in interferon and NF-κB signalling pathways of common carp (Cyprinus carpio L.).BMC veterinary research · 2022Article
- Revisiting the embryogenesis of lip and palate development.Oral diseases · 2022Review
- Mouse models in palate development and orofacial cleft research: Understanding the crucial role and regulation of epithelial integrity in facial and palate morphogenesis.Current topics in developmental biology · 2022Article
- Novel interferon-sensitive genes unveiled by correlation-driven gene selection and systems biology.Scientific reports · 2021Article
- RIPK protein kinase family: Atypical lives of typical kinases.Seminars in cell & developmental biology · 2021Review
- Advances in scarless foetal wound healing and prospects for scar reduction in adults.Cell proliferation · 2020Review
- Article
- Insight Into the Function of RIPK4 in Keratinocyte Differentiation and Carcinogenesis.Frontiers in oncology · 2020Review
- Functional Characterization of a Novel IRF6 Frameshift Mutation From a Van Der Woude Syndrome Family.Frontiers in genetics · 2020Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Receptor-interacting protein kinase 4 (RIPK4) and interferon regulatory factor 6 (IRF6) are critical regulators of keratinocyte differentiation, and their mutation causes the related developmental epidermal disorders Bartsocas-Papas syndrome and popliteal pterygium syndrome, respectively. However, the signaling pathways in which RIPK4 and IRF6 operate to regulate keratinocyte differentiation are poorly defined. Here we identify and mechanistically define a direct functional relationship between RIPK4 and IRF6. Gene promoter reporter and in vitro kinase assays, coimmunoprecipitation experiments, and confocal microscopy demonstrated that RIPK4 directly regulates IRF6 trans-activator activity and nuclear translocation. Gene knockdown and overexpression studies indicated that the RIPK4-IRF6 signaling axis controls the expression of key transcriptional regulators of keratinocyte differentiation, including Grainyhead-like 3 and OVO-like 1. Additionally, we demonstrate that the p.Ile121Asn missense mutation in RIPK4, which has been identified recently in Bartsocas-Papas syndrome, inhibits its kinase activity, thereby preventing RIPK4-mediated IRF6 activation and nuclear translocation. We show, through mutagenesis-based experiments, that Ser-413 and Ser-424 in IRF6 are important for its activation by RIPK4. RIPK4 is also important for the regulation of IRF6 expression by the protein kinase C pathway. Therefore, our findings not only provide important mechanistic insights into the regulation of keratinocyte differentiation by RIPK4 and IRF6, but they also suggest one mechanism by which mutations in RIPK4 may cause epidermal disorders (e.g. Bartsocas-Papas syndrome), namely by the impaired activation of IRF6 by RIPK4.
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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.