Regulation of the Neurospora circadian clock by casein kinase II.
Phosphorylation of clock proteins represents an important mechanism regulating circadian clocks. In Neurospora, clock protein FREQUENCY (FRQ) is progressively phosphorylated over time, and its level decreases when it is extensively phosphorylated. To identify the kinase phosphorylating FRQ and to understand the function of FRQ phosphorylation, a FRQ-phosphorylating kinase was purified and identified as casein kinase II (CKII). Disruption of the catalytic subunit gene of CKII in Neurospora resulted in hypophosphorylation and increased levels of FRQ protein. In addition, the circadian rhythms of frq RNA, FRQ protein, and clock-controlled genes are abolished in the CKII mutant. Our data suggest that the phosphorylation of FRQ by CKII may have at least three functions; it decreases the stability of FRQ, reduces the protein complex formation between FRQ and the WHITE COLLAR proteins, and is important for the closing of the Neurospora circadian negative feedback loop. Taken together, our results suggest that CKII is an important component of the Neurospora circadian clock.
Yang
Yuhong
Y
Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Cheng
Ping
P
Liu
Yi
Y
D001683:Biological Clocks / Q000502:physiology; D047390:Casein Kinase II; D020134:Catalytic Domain / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009491:Neurospora / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C087405:FRQ protein, Neurospora crassa; D005656:Fungal Proteins; D046911:Macromolecular Substances; D012333:RNA, Messenger; D014157:Transcription Factors; C105589:wc-1 protein, Neurospora crassa; C103772:white collar 2 protein, Neurospora; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases