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

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

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)848-856
Number of pages9
JournalOncogene
Volume27
Issue number6
DOIs
Publication statusPublished - 2008 Jan 31

Keywords

  • Apoptosis
  • Epidermis
  • UV
  • p51/p63
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'p51/p63 inhibits ultraviolet B-induced apoptosis via Akt activation'. Together they form a unique fingerprint.

Cite this