FOXO transcription factor-dependent p15INK4b and p19 INK4d expression

Kazuhiro Katayama, A. Nakamura, Yoshikazu Sugimoto, T. Tsuruo, N. Fujita

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1677-1686
Number of pages10
JournalOncogene
Volume27
Issue number12
DOIs
Publication statusPublished - 2008 Mar 13

Fingerprint

Forkhead Transcription Factors
Apoptosis
Cell Cycle Checkpoints
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Gastrin-Secreting Cells
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Cell Nucleus Active Transport
Genetic Promoter Regions
Genes
Transfection
Cell Cycle
Fibroblasts
Cell Proliferation
Population

Keywords

  • Akt
  • FOXO
  • INK4

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

FOXO transcription factor-dependent p15INK4b and p19 INK4d expression. / Katayama, Kazuhiro; Nakamura, A.; Sugimoto, Yoshikazu; Tsuruo, T.; Fujita, N.

In: Oncogene, Vol. 27, No. 12, 13.03.2008, p. 1677-1686.

Research output: Contribution to journalArticle

Katayama, K, Nakamura, A, Sugimoto, Y, Tsuruo, T & Fujita, N 2008, 'FOXO transcription factor-dependent p15INK4b and p19 INK4d expression', Oncogene, vol. 27, no. 12, pp. 1677-1686. https://doi.org/10.1038/sj.onc.1210813
Katayama, Kazuhiro ; Nakamura, A. ; Sugimoto, Yoshikazu ; Tsuruo, T. ; Fujita, N. / FOXO transcription factor-dependent p15INK4b and p19 INK4d expression. In: Oncogene. 2008 ; Vol. 27, No. 12. pp. 1677-1686.
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