From circadian clock gene expression to pathologies.
In most organisms, circadian rhythms are generated by a molecular clockwork involving so-called clock genes. These circadian clock genes participate in regulatory feedback loops, in which proteins regulate their own expression. The outcome is that ribonucleic acids (RNAs) and proteins produced from many of these genes oscillate with a circadian rhythm. Here, we describe the regulation of clock genes and proteins, as deduced from work in rodents. Furthermore, we summarize the work done on human clock genes and their expression in peripheral tissues. Importantly, the research reviewed here points to an implication of clock gene defects in circadian rhythm disorders, including the advanced and delayed sleep phase disorders. Moreover, circadian clock gene dysfunction is likely to be of importance in the development of cancer as well as various other diseases.
Lamont
Elaine Waddington
EW
Douglas Hospital Research Centre, McGill University, Montreal, QC, Canada.
James
Francine O
FO
Boivin
Diane B
DB
Cermakian
Nicolas
N
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks / Q000235:genetics*; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes; D005420:Flavoproteins; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D012890:Sleep / Q000235:genetics*; D012893:Sleep Wake Disorders / Q000235:genetics*; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D005420:Flavoproteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C538960:BMAL1 protein, human; C403671:DELEC1 protein, human; C539022:PER1 protein, human; C421902:PER2 protein, human; C512644:PER3 protein, human; C509769:TIMELESS protein, human; C538943:CLOCK protein, human