PERspective on PER phosphorylation

Abstract

Period (PER) proteins are essential parts of the molecular clocks that control circadian rhythms in flies and mammals. Phosphorylation regulates PER's stability and subcellular localization; however, the physiologically relevant sites have been difficult to identify in spite of knowing the relevant kinase. In this issue of Genes & Development, Chiu and colleagues (1758-1772) identify a key phosphorylation site on PER that recruits the F-box protein Slimb to trigger PER degradation and set clock speed.

Figure 1.

Network regulating PER protein phosphorylation and stability. All of the protein products shown alter circadian rhythms and alter PER phosphorylation and/or stability when mutated in flies. The connectors indicate additional support for the network coming from diverse lines of evidence. See the text for details. The study by Chiu et al. (2008) identified sites on PER phosphorylated by DBT and recognized by Slimb (green lines).

Figure 2.

Dramatic circadian phenotypes from single amino acid changes in PER. The locomotor activity of single flies is shown for three PER variants: PER S47D (left), wild type PER (middle), and PER S47A (right). Flies were monitored in light:dark cycles for the first 3 d of the experiment, before transfer to constant darkness to reveal the free-running periods. per S47D flies have shorter than normal rhythms (∼22 h), compared with ∼23.5 h for control flies. per S47A flies have dramatically long rhythms (∼31 h). See the text for details. The data were kindly provided by Joanna Chiu.