1. ¹Department of Dermatology, Tohoku University, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Japan
2. ²Ikawa Group, Center for Interdisciplinary Research, Tohoku University, Aoba-ku, Sendai, Japan
3. ³Department of Cell Biology, Institute of Development, Aging, and Cancer, Tohoku University, Aoba-ku, Sendai, Japan
4. ⁴Laboratory of Cell Differentiation, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, Japan

Correspondence: Dr S Ikawa, Ikawa Group, Center for Interdisciplinary Research, Tohoku University, Aramaki, 6-3 Aoba, Aoba-ku, Sendai 980-8578, Japan. E-mail: sikawa@cir.tohoku.ac.jp

Received 10 July 2006; Revised 31 October 2006; Accepted 22 November 2006; Published online 22 January 2007.

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 Np51B (Np63), 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, Np51B by itself was found to have ability to induce expression of integrin 64, which promotes attachment of basal cells to basal membrane thereby keeping the cells in immature state. Therefore, we conclude that Np51B expression warrants integrin expression even under the influence of Notch1 and that Np51B 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.