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

R. Okuyama, E. Ogawa, H. Nagoshi, M. Yabuki, A. Kurihara, T. Terui, S. Aiba, M. Obinata, H. Tagami, S. Ikawa

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4478-4488
Number of pages11
JournalOncogene
Volume26
Issue number31
DOIs
Publication statusPublished - 2007 Jul 5

Keywords

  • Keratinocyte
  • Notch
  • Stem cell
  • Tumor suppressor
  • p51/p63
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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