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p51/p63 inhibits ultraviolet B-induced apoptosis via Akt activation

Oncogene volume 27, pages 848–856 (2008)Cite this article

Abstract

The epidermis must be protected against excess apoptotic cell death in response to ultraviolet-B (UV-B) irradiation. p53 is known to be critical for this protection. Although the p53 family member ΔNp51B/ΔNp63α (an N terminal-deleted form of p51/p63) is abundantly expressed in keratinocytes, its contribution to UV-B-dependent apoptosis is largely unknown. We found that, after a transient increase, ΔNp51B is downregulated in UV-B-irradiated keratinocytes undergoing apoptosis, whereas p53 is upregulated with delayed kinetics. Furthermore, the reduction of ΔNp51B by small interfering RNAs augmented UV-B-dependent apoptosis in keratinocytes, indicating that ΔNp51B blocks keratinocyte apoptosis. Although the exogenous expression of ΔNp51B in keratinocytes did not further block the UV-B-dependent apoptosis, to our surprise the expression of TAp51B (an isoform with a full NH2-terminal transactivation domain that is structurally and functionally similar to p53) decreased apoptosis significantly. The blockade of keratinocyte apoptosis by the p51 was dependent on the phosphorylation of Akt, resulting in the activation of a survival pathway. Thus, in addition to its indispensable roles in epithelial development, p51 acts in adult cells to protect the epidermis against UV-B irradiation by preventing excess depletion of keratinocytes.

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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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Author notes

  1. E Ogawa and R Okuyama: These authors contributed equally to this work.

Authors and Affiliations

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

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

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

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

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

    S Ikawa, H Nagoshi, A Kurihara & M Yabuki

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  1. E Ogawa
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  2. R Okuyama
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  3. S Ikawa
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  4. H Nagoshi
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  5. T Egawa
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  7. M Yabuki
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  8. H Tagami
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  9. M Obinata
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  10. S Aiba
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Correspondence to R Okuyama.

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Ogawa, E., Okuyama, R., Ikawa, S. et al. p51/p63 inhibits ultraviolet B-induced apoptosis via Akt activation. Oncogene 27, 848–856 (2008). https://doi.org/10.1038/sj.onc.1210682

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  • DOI: https://doi.org/10.1038/sj.onc.1210682

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