The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis
Open accessAbstract
Linear Ubiquitin chain Assembly Complex (LUBAC) is an E3 ligase complex that generates linear ubiquitin chains and is important for tumour necrosis factor (TNF) signaling activation. Mice lacking Sharpin, a critical subunit of LUBAC, spontaneously develop inflammatory lesions in the skin and other organs. Here we show that TNF receptor 1 (TNFR1)-associated death domain (TRADD)-dependent TNFR1 signaling in epidermal keratinocytes drives skin inflammation in Sharpin-deficient mice. Epidermis-restricted ablation of Fas-associated protein with death domain (FADD) combined with receptor-interacting protein kinase 3 (RIPK3) deficiency fully prevented skin inflammation, while single RIPK3 deficiency only delayed and partly ameliorated lesion development in Sharpin-deficient mice, showing that inflammation is primarily driven by TRADD- and FADD-dependent keratinocyte apoptosis while necroptosis plays a minor role. At the cellular level, Sharpin deficiency sensitized primary murine keratinocytes, human keratinocytes, and mouse embryonic fibroblasts to TNF-induced apoptosis. Depletion of FADD or TRADD in Sharpin-deficient HaCaT cells suppressed TNF-induced apoptosis, indicating the importance of FADD and TRADD in Sharpin-dependent anti-apoptosis signaling in keratinocytes.
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Cites
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Linear ubiquitination prevents inflammation and regulates immune signalling
Gerlach, B., Cordier, S. M., Schmukle, A. C., Emmerich, C. H., Rieser, E., Haas, T. L., Webb, A. I., Rickard, J. A., Anderton, H., Wong, W. W.-L., et al. (2011) · Nature · doi:10.1038/nature09816 · Cited by 940
SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis
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Self-citationSHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex
Tokunaga, F., Nakagawa, T., Nakahara, M., Saeki, Y., Taniguchi, M., Sakata, S.-I., Tanaka, K., Nakano, H., & Iwai, K. (2011) · Nature · doi:10.1038/nature09815 · Cited by 609
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Self-citationProtective Roles for Caspase-8 and cFLIP in Adult Homeostasis
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Cited by
Necroptosis and its role in inflammation
Pasparakis, M., & Vandenabeele, P. (2015) · Nature · doi:10.1038/nature14191 · Cited by 2,148
Self-citationSwatek, K. N., & Komander, D. (2016) · Cell Research · doi:10.1038/cr.2016.39 · Cited by 2,081
Newton, K., Strasser, A., Kayagaki, N., & Dixit, V. M. (2024) · Cell · doi:10.1016/j.cell.2023.11.044 · Cited by 990
Wang, Y., & Kanneganti, T.-D. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.07.038 · Cited by 545
Newton, K., Dugger, D. L., Maltzman, A., Greve, J. M., Hedehus, M., Martin-McNulty, B., Carano, R. A. D., Cao, T. C., van Bruggen, N., Bernstein, L., et al. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2016.46 · Cited by 438
Metadata
- Authors
- Kumari, S., Redouane, Y., Lopez-Mosqueda, J., Shiraishi, R., Romanowska, M., Lutzmayer, S., Kuiper, J., Martinez, C., Dikic, I., Pasparakis, M., & Ikeda, F.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2014-12-02
- Volume
- 3
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W2151861156
- Cited by
- 179
- References
- 8
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis. https://app.cochat.ai/papers/10.7554/elife.03422
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- Kumari, S., Redouane, Y., Lopez-Mosqueda, J., Shiraishi, R., Romanowska, M., Lutzmayer, S., Kuiper, J., Martinez, C., Dikic, I., Pasparakis, M., & Ikeda, F. (2014). Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis. eLife. https://doi.org/10.7554/elife.03422
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