Control mechanism of the circadian clock for timing of cell division in vivo.
Cell division in many mammalian tissues is associated with specific times of day, but just how the circadian clock controls this timing has not been clear. Here, we show in the regenerating liver (of mice) that the circadian clock controls the expression of cell cycle-related genes that in turn modulate the expression of active Cyclin B1-Cdc2 kinase, a key regulator of mitosis. Among these genes, expression of wee1 was directly regulated by the molecular components of the circadian clockwork. In contrast, the circadian clockwork oscillated independently of the cell cycle in single cells. Thus, the intracellular circadian clockwork can control the cell-division cycle directly and unidirectionally in proliferating cells.
Matsuo
Takuya
T
Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
Yamaguchi
Shun
S
Mitsui
Shigeru
S
Emi
Aki
A
Shimoda
Fukuko
F
Okamura
Hitoshi
H
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D056926:CLOCK Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D002940:Circadian Rhythm; D056931:Cryptochromes; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D056744:Cyclin B1; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D007700:Kinetics; D008115:Liver Regeneration; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D010766:Phosphorylation; D017956:Photoreceptor Cells, Invertebrate; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D016203:CDC2 Protein Kinase; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D019926:Cyclin B; D056744:Cyclin B1; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D011505:Protein-Tyrosine Kinases; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; D014157:Transcription Factors; C538961:Bmal1 protein, mouse; C534700:Ccnb1 protein, mouse; C503698:CycB protein, Drosophila; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; C119828:cry protein, Drosophila; C538944:Clock protein, mouse; C499348:Wee1 protein, mouse