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Lookup NU author(s): Professor John CommonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s)Solar UVB light causes damage to the outermost layer of skin. This insult induces rapid local responses, such as dermal inflammation, keratinocyte cell death, and epidermal thickening, all of which have traditionally been associated with DNA damage response signaling. Another stress response that is activated by UVB light is the ribotoxic stress response (RSR), which depends on the ribosome-associated mitogen-activated protein 3 kinases (MAP3K) ZAKα and culminates in p38 and JNK activation. Using ZAK knockout mice, we here show that it is the RSR that is responsible for the early manifestation of UVB-induced skin inflammation and keratinocyte death and subsequent proliferation in vivo. We also show that the RSR controls both p38-mediated pyroptotic and JNK-mediated apoptotic programmed cell death of human keratinocytes in vitro. In sum, our work highlights that skin cells rely on a cytoplasmic and ribosomal stress signal rather than a nuclear and DNA-templated signal for rapid inflammatory responses to UV exposure.
Author(s): Vind AC, Wu Z, Firdaus MJ, Snieckute G, Toh GA, Jessen M, Martinez JF, Haahr P, Andersen TL, Blasius M, Koh LF, Maartensson NL, Common JEA, Gyrd-Hansen M, Zhong FL, Bekker-Jensen S
Publication type: Article
Publication status: Published
Journal: Molecular Cell
Year: 2024
Volume: 84
Issue: 24
Pages: 4774-4789.e9
Print publication date: 19/12/2024
Online publication date: 25/11/2024
Acceptance date: 30/10/2024
Date deposited: 08/01/2025
ISSN (print): 1097-2765
ISSN (electronic): 1097-4164
Publisher: Cell Press
URL: https://doi.org/10.1016/j.molcel.2024.10.044
DOI: 10.1016/j.molcel.2024.10.044
Data Access Statement: RNA sequencing raw data files have been deposited in NCBI’s Gene Expression Omnibus (GEO) archive, with the accession code GEO: GSE251957. d This paper does not report original code. d Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
PubMed id: 39591967
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