Buchumschlag

The CK2 kinase stabilizes CLOCK and represses its activity in the Drosophila circadian oscillator

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Szabó, Áron (VerfasserIn) , Papin, Christian (VerfasserIn) , Zorn, Daniela (VerfasserIn) , Ponien, Prishila (VerfasserIn) , Weber, Frank (VerfasserIn) , Raabe, Thomas (VerfasserIn) , Rouyer, François (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: August 27, 2013
In: PLoS biology
Year: 2013, Jahrgang: 11, Heft: 8, Pages: 1-16
ISSN:1545-7885
DOI:10.1371/journal.pbio.1001645
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pbio.1001645
Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001645
Volltext
Verfasserangaben:Áron Szabó, Christian Papin, Daniela Zorn, Prishila Ponien, Frank Weber, Thomas Raabe, François Rouyer
Beschreibung
Zusammenfassung: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 the activity of the catalytic α subunit of CK2 induces CLK degradation, even in the absence of PER and TIM. Unexpectedly, the regulatory β subunit of the CK2 holoenzyme is not required for the regulation of CLK stability. In addition, downregulation of CK2α 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.
Beschreibung:Gesehen am 27.01.2022
Beschreibung:Online Resource
ISSN:1545-7885
DOI:10.1371/journal.pbio.1001645

Ähnliche Einträge