p53 activity contributes to defective interfollicular epidermal differentiation, in hyperproliferative murine skin
Gollnick, Harald P
Quist, Sven R
British Journal of Dermatology
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Cottle, D., Kretzschmar, K., Gollnick, H. P., & Quist, S. R. (2015). p53 activity contributes to defective interfollicular epidermal differentiation, in hyperproliferative murine skin. British Journal of Dermatology, 174 204-208. https://doi.org/10.1111/bjd.14048
Background- The role of p53 in the pathogenesis of skin diseases such as plaque-type psoriasis has long been questioned but never resolved. Objectives- In this study we set out to determine the contribution of p53 activity to defective interfollicular epidermal skin differentiation in a murine hyperproliferative skin model. Methods- We used the tamoxifen-inducible K14MycER mouse model which exhibits abnormal epidermal differentiation in response to high MYC activity, crossed with p53 knock-out mice. Results- We show that genetic deletion of p53 leads to improvements in granular layer formation. Furthermore, we show that p53 activity regulates down-stream expression of Keratin 6a, Pparb/d and Pparg and is regulated upstream by retinoic acid signalling-dependent mechanisms. Conclusion- We conclude aberrant non-apoptotic p53 activity contributes, in-part, to abnormal differentiation and granular layer defects.
epidermis, skin, psoriasis, parakeratosis, MYC, p53, keratin 6, PPAR, interfollicular epidermis, retinoic acid
This work was supported by the Prof. Fiona M. Watt via the MRC, Wellcome Trust, CRUK, EU FP7 programme, the University of Cambridge, Hutchison Whampoa Ltd. This work was also supported by A/ Prof. Ian M. Smyth and Monash University.
External DOI: https://doi.org/10.1111/bjd.14048
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248966
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Licence URL: http://creativecommons.org/licenses/by/4.0/