Cdk1-FOXO1: a mitotic signal takes center stage in post-mitotic neurons.
An emerging theme in molecular neurobiology is the discovery of post-mitotic functions for proteins classically associated with mitotic transition in cycling cells. Although neurons have departed the cell cycle, they surprisingly express molecules in the cell cycle apparatus throughout development. The major mitotic cyclin-dependent kinase Cdk1 plays a critical role during the period of naturally occurring neuronal death in the nervous system and has been suggested to contribute to the pathogenesis of neurodegenerative diseases. However, the mechanisms by which Cdk1 promotes neuronal apoptosis are incompletely understood. A recent report by Yuan et al., (2008) has identified a direct relationship between this mitotic kinase and forkhead transcription factor FOXO1, a protein previously implicated in cell death, DNA damage repair and tumor suppression. Here we will discuss the key findings of this report and consider the implications of this mechanism to the regulation of other signal transduction pathways in brain development and diseases.
Kim
Albert H
AH
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Bonni
Azad
A
D000595:Amino Acid Sequence; D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D051057:Proto-Oncogene Proteins c-akt; D016203:CDC2 Protein Kinase