Activation of FOXO1 by Cdk1 in cycling cells and postmitotic neurons.

Journal article

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 Ser2...

Expand abstract

Authors: Yuan, Z; Becker, E; Merlo, P; Yamada, T; DiBacco, S

• Publication status: Published
• Journal: Science (New York, N.Y.)
• Volume: 319
• Issue: 5870
• Pages: 1665-1668
• Publication date: 2008-03-01
• DOI: 10.1126/science.1152337
• EISSN: 1095-9203
• ISSN: 0036-8075
• Language: English
• Keywords: Cell Line, Tumor; Apoptosis; Cell Proliferation; Transcription, Genetic; Proto-Oncogene Proteins; Cells, Cultured; NIH 3T3 Cells; Cell Nucleus; Forkhead Transcription Factors; Neurons; Signal Transduction; Cell Cycle Proteins; Humans; Phosphorylation; Mice; Nerve Tissue Proteins; Cell Cycle; Animals; 14-3-3 Proteins; CDC2 Protein Kinase; Rats; Serine; Protein-Serine-Threonine Kinases