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Cellular/Molecular TIMELESS Is an Important Mediator of CK2 Effects on
 

Summary: Cellular/Molecular
TIMELESS Is an Important Mediator of CK2 Effects on
Circadian Clock Function In Vivo
Rose-Anne Meissner, Valerie L. Kilman, Jui-Ming Lin, and Ravi Allada
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208
Circadianoscillationsinclockcomponentsarecentraltogenerationofself-sustained24-hperiodicity.IntheDrosophilamolecularclock,
accumulation, phosphorylation, and degradation of PERIOD (PER) and TIMELESS (TIM) proteins govern period length. Yet little is
known about the kinases that phosphorylate TIM in vivo. It has been shown previously that the protein kinase CK2 phosphorylates TIM
in vitro. Here, we identify a role for CK2 in TIM regulation in vivo. Induction of a dominant-negative CK2 , CK2 Tik
(Tik), increases TIM
protein and tim transcript levels, reduces oscillation amplitude, and results in persistent cytoplasmic TIM localization. Exposure to light
and subsequent TIM degradation results in an increase in the fraction of the transcriptional repressor PER that is nuclear and suppres-
sion of per and tim RNA levels. TIM protein, but not tim transcript, levels are elevated in Tik mutants in a per01
background. In contrast,
Tik effects on PER are undetectable in a tim01
background, suggesting that TIM is required for CK2 effects on PER. To identify potential
CK2 target sites, we assayed TIM phosphorylation rhythms in a deletion mutant that removes a conserved serine-rich domain and found
that TIM protein does not show robust rhythmic changes in mobility by Western blotting, a hallmark of rhythmic phosphorylation. The
periodlengtheningeffectsinTikheterozygotesarereducedinatimUL
mutantthatdisruptsaputativeCK2phosphorylationsite.Together,

  

Source: Allada, Ravi - Department of Neurobiology and Physiology, Northwestern University

 

Collections: Biology and Medicine