Keratinocyte G2/M growth arrest by 1,25-dihydroxyvitamin D3 Is by caused by Cdc2 phosphorylation through Wee1 and Myt1 regulation

Xiuju Dai, Kenshi Yamasaki, Lujun Yang, Koji Sayama, Yuji Shirakata, Sho Tokumara, Yoko Yahata, Mikiko Tohyama, Koji Hashimoto

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

1,25-dihydroxyvitamin D3 (1,25[OH]2VD3) has an antiproliferative effect on keratinocyte growth, and its derivatives are used for the treatment of psoriasis. It was reported previously that 1,25[OH]2VD3 induced cell cycle arrest not only at the G0/G1 phase but also at the G2/M phase. However, the mechanism of 1,25[OH]2VD3-induced G2/M phase arrest in keratinocytes has not been fully understood. The addition of 10-8 to 10-6 M 1,25[OH]2VD3 to cultured normal human keratinocytes enhanced the expression of Myt1 mRNA preceding Wee1 mRNA; 10-6 M 1,25[OH]2VD3 unregulated Myt1 mRNA from 6 h to 24 h and Wee1 mRNA from 12 to 48 h. Interestingly, the levels of phosphorylated Cdc2 were increased between 6 h and 48 h after 1,25[OH]2VD3 treatment, although the expression levels of Cdc2 mRNA and its protein production were reduced. 1,25[OH]2VD3 also decreased the expression of cyclin B1, which forms a complex with Cdc2. These data indicated that the increase of Myt1 and Wee1 induced the phosphorylation of Cdc2 leading to G2/M arrest. In conclusion, the induction of Cdc2 phosphorylation due to the increase of Wee1 and Myt1 as well as the reduction of Cdc2 and cyclin B1 are involved in 1,25[OH] 2VD3-induced G2/M arrest of keratinocytes.

Original languageEnglish
Pages (from-to)1356-1364
Number of pages9
JournalJournal of Investigative Dermatology
Volume122
Issue number6
DOIs
Publication statusPublished - 2004 Jun
Externally publishedYes

Keywords

  • 1,25-dihydroxyvitamin D3
  • Cdc2
  • Cell cycle
  • Keratinocyte
  • Myt1
  • Wee1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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