Activation of FOXO1 by Cdk1 in cycling cells and postmitotic neurons

Zengqiang Yuan, Esther B.E. Becker, Paola Merlo, Tomoko Yamada, Sara DiBacco, Yoshiyuki Konishi, Erik M. Schaefer, Azad Bonni*

*Corresponding author for this work

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Activation of cyclin-dependent kinase 1 (Cdk1) has been linked to cell death of postmitotic neurons in brain development and disease. We found that Cdk1 phosphorylated the transcription factor FOXO1 at Ser249 in vitro and in vivo. The phosphorylation of FOXO1 at Ser249 disrupted FOXO1 binding with 14-3-3 proteins and thereby promoted the nuclear accumulation of FOXO1 and stimulated FOXO1-dependent transcription, leading to cell death in neurons. In proliferating cells, Cdk1 induced FOXO1 Ser249 phosphorylation at the G2/M phase of the cell cycle, resulting in FOXO1-dependent expression of the mitotic regulator Polo-like kinase (Plk). These findings define a conserved signaling link between Cdk1 and FOXO1 that may have a key role in diverse biological processes, including the degeneration of postmitotic neurons.

Original languageEnglish (US)
Pages (from-to)1665-1668
Number of pages4
JournalScience
Volume319
Issue number5870
DOIs
StatePublished - Mar 21 2008

ASJC Scopus subject areas

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    Yuan, Z., Becker, E. B. E., Merlo, P., Yamada, T., DiBacco, S., Konishi, Y., Schaefer, E. M., & Bonni, A. (2008). Activation of FOXO1 by Cdk1 in cycling cells and postmitotic neurons. Science, 319(5870), 1665-1668. https://doi.org/10.1126/science.1152337