ArticleNature communications2018
p63 is a key regulator of iRHOM2 signalling in the keratinocyte stress response.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Targeting iRhom2-mediated PANoptosis ameliorates acute kidney injury.Acta pharmacologica Sinica · 2026Article
- p63 in skin homeostasis and disease: molecular mechanisms and therapeutic potentials.Cell death discovery · 2026Review
- Hepatic Amyloid Beta-42-Metabolizing Proteins in Liver Steatosis and Metabolic Dysfunction-Associated Steatohepatitis.International journal of molecular sciences · 2024Article
- Pachyonychia Congenita: A Research Agenda Leading to New Therapeutic Approaches.The Journal of investigative dermatology · 2024Review
- 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
- Identification of sulforaphane regulatory network in hepatocytes by microarray data analysis based on GEO database.Bioscience reports · 2021Article
- TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development.Cellular and molecular life sciences : CMLS · 2020Review
- iRhom2: An Emerging Adaptor Regulating Immunity and Disease.International journal of molecular sciences · 2020Review
- Emerging perspectives on cytoglobin, beyond NO dioxygenase and peroxidase.Redox biology · 2020Review
- FIH-1 engages novel binding partners to positively influence epithelial proliferation via p63.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders.Frontiers in cardiovascular medicine · 2020Review
- Association of iRhom1 and iRhom2 expression with prognosis in patients with cervical cancer and possible signaling pathways.Oncology reports · 2020Article
- Altered keratinocyte differentiation is an early driver of keratin mutation-based palmoplantar keratoderma.Human molecular genetics · 2019Article
- Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Hyperproliferative keratinocytes induced by trauma, hyperkeratosis and/or inflammation display molecular signatures similar to those of palmoplantar epidermis. Inherited gain-of-function mutations in RHBDF2 (encoding iRHOM2) are associated with a hyperproliferative palmoplantar keratoderma and squamous oesophageal cancer syndrome (termed TOC). In contrast, genetic ablation of rhbdf2 in mice leads to a thinning of the mammalian footpad, and reduces keratinocyte hyperproliferation and migration. Here, we report that iRHOM2 is a novel target gene of p63 and that both p63 and iRHOM2 differentially regulate cellular stress-associated signalling pathways in normal and hyperproliferative keratinocytes. We demonstrate that p63-iRHOM2 regulates cell survival and response to oxidative stress via modulation of SURVIVIN and Cytoglobin, respectively. Furthermore, the antioxidant compound Sulforaphane downregulates p63-iRHOM2 expression, leading to reduced proliferation, inflammation, survival and ROS production. These findings elucidate a novel p63-associated pathway that identifies iRHOM2 modulation as a potential therapeutic target to treat hyperproliferative skin disease and neoplasia.
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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.