FOXO transcription factor-dependent p15INK4b and p19 INK4d expression

K. Katayama, A. Nakamura, Y. Sugimoto, T. Tsuruo, N. Fujita

研究成果: Article査読

54 被引用数 (Scopus)

抄録

FOXO (Forkhead box O) transcription factors are involved in cell-cycle arrest or apoptosis induction by transcripting cell-cycle inhibitor p27 KIP1 or apoptosis-related genes, respectively. Akt/protein kinase B promotes cell proliferation and suppresses apoptosis, in part, by phosphorylating FOXOs. Phosphorylated FOXOs could not exhibit transcriptional activity because of their nuclear export. Here we show that p15INK4b and p19INK4d transcription is associated with FOXO-mediated G 1 cell-cycle arrest. Inhibition of Akt signaling by PI3K inhibitors, a PDK1 inhibitor, or dominant-negative Akt transfection increased expression of p15INK4b and p19INK4d but not p16INK4a and p18INK4c. Ectopic expression of wild type or active FOXO but not inactive form also increased p15INK4b and p19INK4d levels. FOXOs bound to promoter regions and induced transcription of these genes. No increase in the G1-arrested cell population, mediated by PI3K inhibitor LY294002, was observed in INK4b-/- or INK4d-/- murine embryonic fibroblasts. In summary, FOXOs are involved in G1 arrest caused by Akt inactivation via p15INK4b and p19 INK4d transcription.

本文言語English
ページ(範囲)1677-1686
ページ数10
ジャーナルOncogene
27
12
DOI
出版ステータスPublished - 2008 3月 13

ASJC Scopus subject areas

  • 分子生物学
  • 遺伝学
  • 癌研究

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