Document Type
Article
Publication Date
1-4-2000
Publication Title
Proceedings of the National Academy of Sciences of the United States of America
Department
Geisel School of Medicine
Abstract
Under free running conditions, FREQUENCY (FRQ) protein, a central component of the Neurospora circadian clock, is progressively phosphorylated, becoming highly phosphorylated before its degradation late in the circadian day. To understand the biological function of FRQ phosphorylation, kinase inhibitors were used to block FRQ phosphorylation in vivo and the effects on FRQ and the clock observed. 6-dimethylaminopurine (a general kinase inhibitor) is able to block FRQ phosphorylation in vivo, reducing the rate of phosphorylation and the degradation of FRQ and lengthening the period of the clock in a dose-dependent manner. To confirm the role of FRQ phosphorylation in this clock effect, phosphorylation sites in FRQ were identified by systematic mutagenesis of the FRQ ORF. The mutation of one phosphorylation site at Ser-513 leads to a dramatic reduction of the rate of FRQ degradation and a very long period (>30 hr) of the clock. Taken together, these data strongly suggest that FRQ phosphorylation triggers its degradation, and the degradation rate of FRQ is a major determining factor for the period length of the Neurospora circadian clock.
DOI
10.1073/pnas.97.1.234
Original Citation
Liu Y, Loros J, Dunlap JC. Phosphorylation of the Neurospora clock protein FREQUENCY determines its degradation rate and strongly influences the period length of the circadian clock. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):234-9. doi: 10.1073/pnas.97.1.234. PMID: 10618401; PMCID: PMC26646.
Dartmouth Digital Commons Citation
Liu, Yi; Loros, Jennifer; and Dunlap, Jay C., "Phosphorylation of the Neurospora Clock Protein FREQUENCY Determines its Degradation Rate and Strongly Influences the Period Length of the Circadian Clock" (2000). Dartmouth Scholarship. 1509.
https://digitalcommons.dartmouth.edu/facoa/1509
