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The CK2 Kinase Stabilizes CLOCK and Represses Its Activity in the Drosophila Circadian Oscillator

Please always quote using this URN: urn:nbn:de:bvb:20-opus-127234
  • Phosphorylation is a pivotal regulatory mechanism for protein stability and activity in circadian clocks regardless of their evolutionary origin. It determines the speed and strength of molecular oscillations by acting on transcriptional activators and their repressors, which form negative feedback loops. In Drosophila, the CK2 kinase phosphorylates and destabilizes the PERIOD (PER) and TIMELESS (TIM) proteins, which inhibit CLOCK (CLK) transcriptional activity. Here we show that CK2 also targets the CLK activator directly. Downregulating thePhosphorylation is a pivotal regulatory mechanism for protein stability and activity in circadian clocks regardless of their evolutionary origin. It determines the speed and strength of molecular oscillations by acting on transcriptional activators and their repressors, which form negative feedback loops. In Drosophila, the CK2 kinase phosphorylates and destabilizes the PERIOD (PER) and TIMELESS (TIM) proteins, which inhibit CLOCK (CLK) transcriptional activity. Here we show that CK2 also targets the CLK activator directly. Downregulating the activity of the catalytic alpha subunit of CK2 induces CLK degradation, even in the absence of PER and TIM. Unexpectedly, the regulatory beta subunit of the CK2 holoenzyme is not required for the regulation of CLK stability. In addition, downregulation of \(CK2\alpha\) activity decreases CLK phosphorylation and increases per and tim transcription. These results indicate that CK2 inhibits CLK degradation while reducing its activity. Since the CK1 kinase promotes CLK degradation, we suggest that CLK stability and transcriptional activity result from counteracting effects of CK1 and CK2.show moreshow less

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Metadaten
Author: Áron Szabó, Christian Papin, Daniela Zorn, Prishila Ponien, Frank Weber, Thomas Raabe, François Rouyer
URN:urn:nbn:de:bvb:20-opus-127234
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Medizinische Strahlenkunde und Zellforschung
Language:English
Parent Title (English):PLoS Biology
ISSN:1545-7885
Year of Completion:2013
Volume:11
Issue:8
Pagenumber:e1001645
Source:PLoS Biology 11(8): e1001645. doi:10.1371/journal.pbio.1001645
DOI:https://doi.org/10.1371/journal.pbio.1001645
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:CT, circadian time; DD, constant darkness; LD, light:dark; PER-TIM complex; behavioral rhythms; beta-subunit; gene; in-vivo; negative feedback loop; phosphorylation; posttranslational regulation; proteins period; transcription factor
Release Date:2016/03/03
EU-Project number / Contract (GA) number:18741
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung