High-throughput screening and chemical biology: new approaches for understanding circadian clock mechanisms.
Most organisms exhibit daily changes in physiology and metabolism under the control of a cell-autonomous circadian clock. In the core clock mechanism, clock genes form a transcription factor network to generate circadian rhythms of gene expression. Clock protein phosphorylation and histone modifications are also important for the clock regulation. Pharmacological approaches have been making significant contributions to the clock research, for example, in characterizing the roles of protein kinases CKIdelta, CKIepsilon, CK2, and GSK-3beta. Recently, high-throughput circadian functional assays have been established. Chemical biology approaches utilizing high-throughput compound screening together with RNAi-based genomic screening will open a new way for the circadian clock field. Finding a set of compounds that potently affect the clock function will lead to the identification of novel clock components and form the basis for therapeutic strategies directed toward circadian disorders.
Cell and Developmental Biology, Division of Biological Sciences, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Tsuyoshi
T
Hirota
Steve A
SA
Kay
D001683:Biological Clocks / Q000235:genetics*; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D006657:Histones / Q000378:metabolism; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D006657:Histones; D047428:Protein Kinase Inhibitors; D014157:Transcription Factors; D056926:CLOCK Proteins; D017346:Protein Serine-Threonine Kinases