Negative regulation of forkhead transcription factor AFX (Foxo4) by CBP-induced acetylation

  • Authors:
    • Masahiro Fukuoka
    • Hiroaki Daitoku
    • Mitsutoki Hatta
    • Hitomi Matsuzaki
    • Satoshi Umemura
    • Akiyoshi Fukamizu
  • View Affiliations

  • Published online on: Wednesday, October 1, 2003
  • Pages: 503-508
  • DOI: 10.3892/ijmm.12.4.503

Abstract

AFX (also called Foxo4), a member of mammalian FOXO forkhead transcription factors, is the homolog of DAF-16, which contributes longevity and oxidative stress in Caenorhabditis elegans. Here, we show that CREB-binding protein (CBP) interacts with AFX via CH1 region and acetylates it at the three lysine residues (K186, K189, and K408). Trichostatin A (TSA) repressed the AFX-stimulated transcription, and substitution of the lysine residues with arginine (K186, 189, 408R) enhanced the transcriptional activity of AFX. Furthermore, TSA suppressed the expression of p27kip1 gene induced by AFX in HEK293T cells. Compared to the coexpression of CBP wild-type, a HAT activity-deficient mutant (ΔHAT) efficiently leads the cooperative activation of AFX transcription in HepG2 cells. Taken together, these results demonstrate that CBP-induced acetylation of AFX is a novel modification mechanism by which AFX keeps the transcriptional activity mitigating in the nucleus.
Journal Cover

October 2003
Volume 12 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

2013 Impact Factor: 1.88
Ranked #27/122 Medicine Research and Experimental
(total number of cites)

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APA
Fukuoka, M., Daitoku, H., Hatta, M., Matsuzaki, H., Umemura, S., & Fukamizu, A. (2003). Negative regulation of forkhead transcription factor AFX (Foxo4) by CBP-induced acetylation. International Journal of Molecular Medicine, 12(4), 503-508.
MLA
Fukuoka, Daitoku, Hatta, Matsuzaki, Umemura, and Akiyoshi Fukamizu. "Negative regulation of forkhead transcription factor AFX (Foxo4) by CBP-induced acetylation." International Journal of Molecular Medicine International Journal of Molecular Medicine 12.4 (2003): 503-508.
Chicago
Fukuoka, Daitoku, Hatta, Matsuzaki, Umemura, and Akiyoshi Fukamizu. "Negative regulation of forkhead transcription factor AFX (Foxo4) by CBP-induced acetylation." International Journal of Molecular Medicine International Journal of Molecular Medicine 12 no. 4 (2003): 503-508.