RNF31 Regulates Skin Homeostasis by Protecting Epidermal Keratinocytes from Cell Death
| Autor: | Hailin Tu, Mingchao Wang, Xin Lin, Xueqiang Zhao, Guangna Liu, Lin Li, Yong Tang, Guoxing Zheng |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Keratinocytes
0301 basic medicine Programmed cell death Ubiquitin-Protein Ligases Protein subunit Immunology Apoptosis Inflammation Mice 03 medical and health sciences Ubiquitin In vivo medicine Animals Homeostasis Immunology and Allergy Skin Mice Knockout Cell Death biology Tumor Necrosis Factor-alpha Chemistry NF-kappa B Ubiquitination TNF Receptor-Associated Factor 1 Cell biology Mice Inbred C57BL 030104 developmental biology biology.protein Tumor necrosis factor alpha Epidermis medicine.symptom Signal Transduction |
| Zdroj: | The Journal of Immunology. 200:4117-4124 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1800172 |
| Popis: | Linear ubiquitin chain assembly complex plays an important role in regulating TNF-α signaling activation by modifying target proteins with linear (M1-linked) ubiquitin chains. In this study, we report that the epidermis-specific knockout (KO) of RNF31, the catalytic subunit of linear ubiquitin chain assembly complex, results in an early postnatal lethality in mice due to severe skin inflammation. The inflammation was mainly triggered by TNF-α–induced apoptosis in RNF31 KO keratinocytes. Mechanistically, the deficiency of RNF31 not only impaired TNF-α–induced NF-κB activation, but also significantly increased apoptosis. Consistently, deleting TNF receptor 1 could rescue the lethality of RNF31 epidermis-specific KO mice and also the skin inflammation. Collectively, our study provides an in vivo insight that linear ubiquitination is critical for maintaining the homeostasis of keratinocytes, which will shed light on designing therapeutic compounds to treat skin inflammation. |
| Databáze: | OpenAIRE |
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