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p53 homologue, p51/p63, maintains the immaturity of keratinocyte stem cells by inhibiting Notch1 activity

Oncogene volume 26, pages 4478–4488 (2007)Cite this article

Abstract

p53 homologue, p51/p63, predominantly expressed in keratinocyte stem cells, is indispensable for the formation of epidermis. Notch1, another such gene indispensable for the process, induces growth arrest and differentiation in keratinocytes. We found that exogenous expression of ΔNp51B (ΔNp63α), one of the isoforms of p51 specifically expressed in basal keratinocytes, blocked Notch 1-dependent growth arrest and differentiation in mouse keratinocytes by inhibiting p21 expression and maintaining integrins expression. Furthermore, ΔNp51B by itself was found to have ability to induce expression of integrin α6β4, which promotes attachment of basal cells to basal membrane thereby keeping the cells in immature state. Therefore, we conclude that ΔNp51B expression warrants integrin expression even under the influence of Notch1 and that ΔNp51B is a long-sought factor required to maintain basal cell keratinocytes immaturity by inhibiting Notch1 activity. We will postulate a plausible model explaining the maintenance of the squamous epithelium architectures as well as offering mechanistic explanations for pathological features of skin diseases, including cancers, psoriasis along with physiological wound healings.

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Acknowledgements

This study was partly supported by a Grant in Aid from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese government.

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Authors and Affiliations

  1. Department of Dermatology, Tohoku University, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Japan

    R Okuyama, E Ogawa, T Terui, S Aiba & H Tagami

  2. Ikawa Group, Center for Interdisciplinary Research, Tohoku University, Aoba-ku, Sendai, Japan

    H Nagoshi, M Yabuki, A Kurihara, M Obinata & S Ikawa

  3. Department of Cell Biology, Institute of Development, Aging, and Cancer, Tohoku University, Aoba-ku, Sendai, Japan

    H Nagoshi, M Yabuki, A Kurihara & S Ikawa

  4. Laboratory of Cell Differentiation, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, Japan

    M Obinata & S Ikawa

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  1. R Okuyama
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  2. E Ogawa
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Correspondence to S Ikawa.

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Okuyama, R., Ogawa, E., Nagoshi, H. et al. p53 homologue, p51/p63, maintains the immaturity of keratinocyte stem cells by inhibiting Notch1 activity. Oncogene 26, 4478–4488 (2007). https://doi.org/10.1038/sj.onc.1210235

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